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Print | Back Treatment and prognosis of acute bacterial meningitis in children older than one month of age Author Sheldon L Kaplan MD Section Editors Morven S Edwards MD Douglas R Nordli Jr MD Deputy Editor Mary M Torchia MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete Literature review current through Aug 2013 | This topic last updated Apr 2 2013
INTRODUCTION mdash Suspected bacterial meningitis is a medical emergency and immediate
diagnostic steps must be taken to establish the specific cause so that appropriate
antimicrobial therapy can be initiated The mortality rate of untreated bacterial meningitis
approaches 100 percent and even with optimal therapy morbidity and mortality may occur
Neurologic sequelae are common among survivors
The treatment and prognosis of bacterial meningitis in infants and children older than one
month will be reviewed here The pathogenesis epidemiology clinical features and diagnosis
of acute bacterial meningitis and the treatment and prognosis of bacterial meningitis in
neonates (lt1 month of age) and adults are discussed separately (See Pathogenesis and
pathophysiology of bacterial meningitis and Clinical features and diagnosis of acute
bacterial meningitis in children older than one month of age and Treatment and outcome of
bacterial meningitis in the neonate and Initial therapy and prognosis of bacterial meningitis
in adults and Treatment of bacterial meningitis caused by specific pathogens in adults)
GENERAL PRINCIPLES mdash There are a number of general principles of antibiotic therapy in
patients with bacterial meningitis The most important initial issues are avoidance of delay in
administering therapy and the choice of drug regimen
Avoidance of delay mdash Antibiotic therapy should be initiated immediately after lumbar
puncture (LP) is performed if the clinical suspicion for meningitis is high (algorithm 1) Delay in
the administration of appropriate antibiotics can have a deleterious effect on outcome for
patients who are deteriorating rapidly
If computed tomography (CT) scan is to be performed before LP antibiotic therapy should be
initiated immediately after blood cultures are obtained Although the administration of
antimicrobial therapy before LP may affect the yield of cerebrospinal fluid (CSF) Gram stain
and culture pathogens other than meningococcus usually can be identified in the CSF up to
several hours after the administration of antibiotics [1-3] (See Clinical features and diagnosis
of acute bacterial meningitis in children older than one month of age section on
Interpretation of CSF in pretreated patients)
Antibiotic regimen mdash There are two general principles of antibiotic therapy for bacterial
meningitis [4]
The agent(s) used must be bactericidal against the infecting organism
The agent(s) used must be able to penetrate past the blood-brain barrier to reach a
sufficient concentration in the CSF
Bactericidal agents mdash Since the CSF is a site of impaired humoral immunity a fundamental
principle of therapy of bacterial meningitis is that antibiotics must achieve a bactericidal effect
within CSF to result in optimal microbiologic cure [56] This principle is supported by clinical
observations of poor outcomes in patients receiving bacteriostatic therapy (eg clindamycin
tetracycline) [7] as well as direct experimental evidence in which bactericidal antibiotic
therapy resulted in optimal microbiologic cure and survival in animals with pneumococcal
meningitis [8]
Chloramphenicol is a bacteriostatic drug for most enteric Gram-negative rods however it
usually is bactericidal for Haemophilus influenzae Neisseria meningitidis and Streptococcus
pneumoniae and has been used extensively and successfully to treat meningitis caused by
these organisms
Drug entry into CSF mdash Treatment of bacterial meningitis requires adequate concentration of
antibiotics in the CSF Most drugs reach peak concentrations in the CSF that are only 10 to
20 percent of peak concentrations in the serum This is because the blood-brain barrier
blocks macromolecule entry into the CSF with small lipophilic molecules penetrating most
easily
The peak concentration of drugs in CSF increases with inflammation of the blood-brain
barrier This was illustrated in one study that sequentially monitored CSF and serum penicillin
levels in children with bacterial meningitis The mean CSFserum ratio two hours after
administration of the same intravenous dose of penicillin was 42 percent on the first day of
therapy but fell to less than 10 percent on the 10th day when the inflammatory changes had
subsided [9] (See Cerebrospinal fluid Physiology and utility of an examination in disease
states section on Blood-brain barrier)
Because of the general limitation in antibiotic penetration into the CSF all patients should be
treated with intravenous antibiotics Oral antibiotics should be avoided since the dose and
tissue levels tend to be considerably lower than with parenteral agents One exception can be
made for chloramphenicol which has been administered successfully by the oral route to
treat H influenzae type b (Hib) meningitis in children [10]
Choice of regimen mdash The choice of regimen depends upon whether the pathogen is known
since regimens for empiric therapy pose a different set of management issues than do those
used to treat known pathogens (See Empiric therapy below and Specific therapy below)
PRETREATMENT EVALUATION mdash If possible the pretreatment evaluation of children with
suspected bacterial meningitis should include a complete history and physical examination
cerebrospinal fluid (CSF) examination (cell count and differential glucose protein Gram stain
and culture) complete blood count (CBC) with differential and platelet count two aerobic
blood cultures serum electrolytes glucose blood urea nitrogen and creatinine evaluation of
clotting function is especially indicated if petechiae or purpuric lesions are noted (algorithm 1)
In cases in which the performance of a lumbar puncture (LP) is delayed by rapidly
deteriorating clinical status or the need for neuroimaging blood cultures should be obtained
before the administration of antibiotic therapy (algorithm 1)
The pretreatment evaluation of infants and children with suspected bacterial meningitis is
discussed in greater detail separately (See Clinical features and diagnosis of acute bacterial
meningitis in children older than one month of age section on Evaluation)
IMMEDIATE MANAGEMENT mdash Immediate management of children with suspected bacterial
meningitis includes [11]
Assurance of adequate ventilation and cardiac perfusion (see Initial assessment and
stabilization of children with respiratory or circulatory compromise)
Initiation of hemodynamic monitoring and support at the same time as obtaining
appropriate laboratory studies (blood and cerebrospinal fluid [CSF]) (see
Pretreatment evaluation above)
Establishment of venous access (see Vascular (venous) access for pediatric
resuscitation and other pediatric emergencies)
Administration of fluids as necessary to treat septic shock if present (see Systemic
inflammatory response syndrome (SIRS) and sepsis in children Definitions
epidemiology clinical manifestations and diagnosis)
Administration of dexamethasone if warranted after assessment of potential benefits
and risks before or immediately after the first dose of antimicrobial therapy (see
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
Administration of the first dose of empiric antibiotics (vancomycin [15 mgkg] plus
either cefotaxime [100 mgkg] or ceftriaxone [50 mgkg]) (see Empiric regimen
below)
Administration of glucose (025 gkg) for documented hypoglycemia (serum glucose
concentration less than 40 mgdL [22 mmolL]) (see Approach to hypoglycemia in
infants and children section on Glucose therapy)
Treatment of acidosis and coagulopathy if present (see Systemic inflammatory
response syndrome (SIRS) and sepsis in children Definitions epidemiology clinical
manifestations and diagnosis and Disseminated intravascular coagulation in infants
and children)
SUPPORTIVE CARE
Fluid management mdash Careful management of fluid and electrolyte balance is an important
aspect of supportive therapy Both over- and under-hydration are associated with adverse
outcomes [12]
Children who are in shock should receive sufficient quantities of isotonic fluid to maintain
blood pressure and cerebral perfusion [13] The management of septic shock in children is
discussed separately (See Systemic inflammatory response syndrome (SIRS) and sepsis in
children Definitions epidemiology clinical manifestations and diagnosis)
Children who are hypovolemic but not in shock should be rehydrated with careful and
frequent attention to fluid status Body weight urine volume and specific gravity and serum
electrolytes should be monitored regularly (See Treatment of hypovolemia (dehydration) in
children)
For children who are neither in shock nor hypovolemic we suggest moderate fluid restriction
(1200 mLm2 per day) initially especially if the serum sodium is less than 130 mEqL until
evidence of inappropriate secretion of antidiuretic hormone can be excluded Body weight
urine volume and specific gravity serum electrolytes and if indicated serum and urine
osmolalities should be carefully monitored Fluid administration can be liberalized gradually
as the serum sodium reaches 135 mEqL Most children can receive maintenance fluid intake
within 24 hours of hospitalization
Monitoring mdash Children who are being treated for bacterial meningitis should be monitored
carefully for complications (eg increased intracranial pressure seizure activity development
of infected subdural effusions) particularly during the first two to three days of treatment
when complications are most likely to occur [13-15]
Heart rate blood pressure and respiratory rate should be monitored regularly with a
frequency appropriate to the care setting
A complete neurologic examination should be performed daily rapid assessment of
neurologic function should be performed several times per day for the first several
days of treatment
Head circumference should be measured daily in children younger than 18 months
EMPIRIC THERAPY mdash The organism causing bacterial meningitis seldom is known at the
outset of therapy as a result an empiric treatment plan usually needs to be formulated An
awareness of the most likely pathogens knowledge of local susceptibility patterns and
assessment of the degree of urgency are necessary to devise an optimal empiric treatment
strategy Once culture results are available treatment should be modified to follow the
guidelines for specific pathogens (See Specific therapy below)
Major pathogens mdash The two most common causes of bacterial meningitis in infants and
children who have received a full series of H influenzae type b (Hib) and pneumococcal
conjugate vaccines are S pneumoniae and N meningitidis [16] Among S pneumoniae
isolates antibiotic resistance remains a concern In developing countries that do not routinely
immunize against Hib Hib continues to be a frequent cause of meningitis [17] (See Clinical
features and diagnosis of acute bacterial meningitis in children older than one month of age
section on Epidemiology)
Group B streptococcus Escherichia coli and Listeria monocytogenes are important causes in
infants younger than three months (See Clinical features and diagnosis of acute bacterial
meningitis in children older than one month of age section on Epidemiology and Clinical
features and diagnosis of bacterial meningitis in the neonate section on Etiology)
Empiric regimen mdash The empiric regimen should include coverage for penicillin-resistant S
pneumoniae and N meningitidis the two most common causes of bacterial meningitis in
infants and children Additional coverage for other organisms may be indicated in children
with immune deficiency recent neurosurgery penetrating head trauma and anatomic
defects The cerebrospinal fluid (CSF) Gram stain may provide important clues for the need to
add additional antibiotics to cover for more unusual organisms Broad-spectrum antimicrobial
therapy should be continued until CSF culture results are available because Gram stain
results are subject to observer misinterpretation [18] (See Special circumstances below)
An appropriate empiric regimen (ie one that covers antibiotic-resistant S pneumoniae N
meningitidis and Hib) includes high doses of a third-generation cephalosporin (eg
cefotaxime ceftriaxone) and vancomycin [19]
Cefotaxime 300 mgkg per day intravenously (IV) (maximum dose 12 gday) in 3 or 4
divided doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2
divided doses plus
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses
If ceftriaxone is used we suggest twice daily dosing to avoid the possibility of inadequate
treatment in the event of dosing errors delayed doses or missed doses [13] Some experts
suggest the addition of rifampin to the empiric regimen if dexamethasone is administered [18]
(See Pneumococcal meningitis in children section on Empiric therapy)
Consultation with an expert in pediatric infectious diseases is recommended for children in
whom cephalosporins or vancomycin are contraindicated
Use of dexamethasone mdash Issues related to neurologic sequelae after bacterial meningitis
and the possible role of dexamethasone therapy to minimize these complications are
discussed separately (See Neurologic complications of bacterial meningitis in children and
Dexamethasone and other measures to prevent neurologic complications of bacterial
meningitis in children section on Dexamethasone)
The decision to use dexamethasone in children with suspected bacterial meningitis must be
individualized Factors to be weighed in this decision include
The etiologic agent
The ability to administer dexamethasone before or within 1 hour of the first dose of
antibiotic therapy
The empiric antibiotic regimen
The potential adverse effects
The American Academy of Pediatrics (AAP) Committee on Infectious Diseases suggests that
dexamethasone therapy may be beneficial in children with Hib meningitis if given before or at
the same time as the first dose of antimicrobial therapy [20] The AAP Committee on
Infectious Diseases suggests that dexamethasone therapy be considered for infants and
children older than six weeks with pneumococcal meningitis after weighing the potential risks
and benefits [21]
In accordance with the AAP Committee on Infectious Diseases we recommend adjunctive
therapy with dexamethasone for children with Hib meningitis We suggest that decisions
regarding the use of dexamethasone in children with pneumococcal meningitis or in those in
whom bacterial meningitis is suspected but the etiology unknown be individualized
depending upon careful analysis of the potential risks and benefits The author of this topic
review usually does not administer dexamethasone to children with suspected pneumococcal
or meningococcal meningitis In the same patients other experts may choose to use
dexamethasone (See Pneumococcal meningitis in children section on Dexamethasone)
Regimen mdash If the decision is made to use dexamethasone dexamethasone should be given
before or concurrently with the first dose of the antimicrobial agent(s) it is probably of no
benefit if given more than 1 hour later [18] The regimen for dexamethasone is
Dexamethasone 015 mgkg per dose every 6 hours for 2 to 4 days [13] Two days of
dexamethasone appear to be as effective as and less toxic than longer courses [22]
Special circumstances mdash The treatment of bacterial meningitis in children with immune
deficiency recent neurosurgery anatomic defects penetrating head trauma CSF leak and
during epidemics requires consultation with an expert in pediatric infectious diseases
Immune deficiency mdash Vancomycin plus either cefotaxime or ceftriaxone given as described
above are reasonable empiric coverage for most children with an underlying defect in host
defense (See Empiric regimen above)
If a Gram-negative rod is observed on Gram stain of the CSF the addition of an
aminoglycoside (eg gentamicin amikacin) to these two agents is recommended (See Gram-
negative rods below)
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 22 5 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Peak and trough serum concentrations must be monitored when aminoglycosides are used
[23]
Cancer and neutropenia mdash In a retrospective case series of 40 cases of bacterial or fungal
meningitis in 36 neutropenic pediatric cancer patients (two-thirds of whom had recent
neurosurgery a central nervous system [CNS] device or CSF leak) S pneumoniae and
Staphylococcus aureus were the two most common isolates [24] Empiric therapy in such
patients should be based upon the Gram stain results Initial therapy typically includes
vancomycin plus an aminoglycoside plus either cefotaxime or ceftriaxone If there is any
concern about Pseudomonas aeruginosa or an increased risk for infection caused by an
extended-spectrum beta-lactamase (ESBL)-producing organism meropenem may be
warranted as an alternative to cefotaxime or ceftriaxone
T cell defects mdash S pneumoniae and L monocytogenes are the most likely causes of
bacterial meningitis in patients with defective cell-mediated immunity [25] To address these
pathogens the empiric regimen for children with defects in T cell immunity should include
vancomycin plus either cefotaxime or ceftriaxone dosed as recommended above and high-
dose ampicillin (see Empiric regimen above) The dose of ampicillin is as follows
Ampicillin 300 to 400 mgkg IV per day (maximum dose 10 to 12 gday) in 4 or 6
divided doses
Recent neurosurgery mdash In addition to the usual nosocomial pathogens that may complicate
any surgical procedure coagulase-negative staphylococci (such as Staphylococcus
epidermidis) and S aureus are important causes of meningitis in patients who have had
recent neurosurgery Patients who undergo operations that involve a prosthetic device such
as a ventricular shunt or drain are clearly at risk for developing infection (See Infections of
central nervous system shunts and other devices)
Patients who have undergone recent neurosurgery also are at increased risk for meningitis
with enteric Gram-negative rods such as E coli and Klebsiella species as well as P
aeruginosa (See Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in this setting usually consists of a combination of a third-generation
cephalosporin and vancomycin In addition an aminoglycoside (eg gentamicin amikacin)
should be added if Gram-negative bacilli are noted on CSF Gram stain
Alternative regimens include
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
The local antibiogram can help to guide which of the agents directed against Gram-
negative organisms might be most appropriate (eg a high rate of resistance to
ceftazidime suggests meropenem is a better choice)
Recent placement of CSF shunt mdash In infants and children who have had recent placement
of a CSF shunt vancomycin plus either cefotaxime or ceftriaxone are recommended [18]
Anatomic defects mdash Children with anatomic defects (eg dermal sinus (picture 1) urinary
tract anomalies) are at increased risk for meningitis with S aureus or coagulase-negative
staphylococcus and enteric Gram-negative rods such as E coli and Klebsiella (See
Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in children with anatomic defects should include vancomycin plus either
cefotaxime or ceftriaxone dosed as recommended above (See Empiric regimen above)
In addition an aminoglycoside (eg gentamicin amikacin) should be added if Gram-negative
bacilli are noted on CSF Gram stain
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 225 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Penetrating head trauma mdash Patients with penetrating head trauma are at risk for meningitis
with S aureus coagulase-negative staphylococci (such as S epidermidis) and aerobic
Gram-negative bacilli including P aeruginosa [18]
Empiric therapy in this setting usually consists of a combination of vancomycin plus an
extended-spectrum cephalosporin (cefepime or ceftazidime) or meropenem plus an
aminoglycoside [18]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
plus
Gentamicin 75 mgkg per day IV in 3 divided doses or amikacin 15 to 225 mgkg per
day IV (maximum dose 15 gday) in 3 divided doses
CSF leak mdash Patients with a CSF leak (CSF rhinorrhea or otorrhea) should be treated for
presumed pneumococcal meningitis since S pneumoniae is the most likely organism in this
setting Pneumococcal meningitis in these patients is usually less severe than that caused by
hematogenous invasion and the prognosis is somewhat better Nevertheless because of the
possibility of an isolate highly resistant to penicillin such patients should be treated with a
third-generation cephalosporin plus vancomycin until culture results return This regimen
also will cover H influenzae which rarely causes meningitis in patients with dural defects
(See Empiric regimen above)
Epidemics mdash The empiric treatment of bacterial meningitis during epidemics in which N
meningitidis is suspected is discussed separately (See Treatment and prevention of
meningococcal infection)
SPECIFIC THERAPY mdash Once the causative agent and its in vitro antimicrobial susceptibility
pattern are known empiric antimicrobial therapy can be altered accordingly
S pneumoniae mdash The treatment of pneumococcal meningitis is discussed in detail
separately (See Pneumococcal meningitis in children section on Overview of treatment)
Therapeutic options for pneumococcal meningitis according to antibiotic susceptibility profiles
are outlined in the table (table 1) The usual duration of therapy in uncomplicated cases of S
pneumoniae meningitis is 10 to 14 days
N meningitidis mdash Meningococcal meningitis is best treated with penicillin
Penicillin G 250000 to 300000 Ukg per day IV (maximum 24 million Uday) in 4 or 6
divided doses
A third-generation cephalosporin is an effective alternative to penicillin for children with
penicillin allergy that is not characterized by anaphylaxis [2627] (See Allergy to penicillins
and Penicillin-allergic patients Use of cephalosporins carbapenems and monobactams)
Possible regimens include
Cefotaxime 225 to 300 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided
doses or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
For patients with penicillin allergy characterized by anaphylaxis chloramphenicol is a
recommended alternative [27] Desensitizing the patient to the third-generation cephalosporin
is another option
Chloramphenicol 75 to 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4
divided doses
Although scattered cases of N meningitidis resistant to penicillin have been reported such
strains are rare Relative resistance to penicillin occurs more commonly but does not have an
impact on the response to penicillin or cephalosporin therapy [2829] (See Treatment and
prevention of meningococcal infection section on Penicillin)
A five- to seven-day duration of therapy is adequate for meningococcal meningitis and
eradication of the organism from the cerebrospinal fluid (CSF) [27] However neither penicillin
nor chloramphenicol therapy reliably eradicates nasopharyngeal carriage of N meningitidis
Patients treated with penicillin or chloramphenicol should receive antimicrobial therapy to
eradicate nasopharyngeal carriage before hospital discharge to prevent transmission of the
organism to contacts (See Treatment and prevention of meningococcal infection section on
Antimicrobial chemoprophylaxis)
H influenzae type b mdash Ceftriaxone or cefotaxime is the treatment of choice for ampicillin-
resistant H influenzae type b (Hib) meningitis [2030-32]
Cefotaxime 200 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided doses
or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
Ampicillin is effective for susceptible strains
Ampicillin 300 to 400 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6
divided doses
For patients with penicillin allergy characterized by anaphylaxis desensitizing the patient is
one option Chloramphenicol is another
Chloramphenicol 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4 divided
doses
Cefuroxime should not be used to treat Hib meningitis because it is associated with less
rapid sterilization of the CSF and a greater incidence of hearing loss [3031]
Patients with Hib meningitis should be treated for 7 to 10 days Pharyngeal colonization
persists after curative therapy with agents other than ceftriaxone and cefotaxime Patients
who are not treated with ceftriaxone or cefotaxime should receive rifampin before hospital
discharge to prevent transmission of the organism to contacts For patients who are treated
with chloramphenicol rifampin therapy should be delayed until chloramphenicol is
discontinued since concomitant administration of rifampin may reduce serum concentrations
of chloramphenicol [33] (See Prevention of Haemophilus influenzae infection section on
Antibiotic prophylaxis of close contacts)
L monocytogenes mdash L meningitis traditionally has been treated with ampicillin and
gentamicin because resistance to these drugs is quite rare [34] Although gentamicin has
poor CSF penetration it is used for synergy [35]
Ampicillin 300 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative for penicillin-allergic patients
[36] The dose for TMP-SMX is as follows
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses
Meropenem a carbapenem approved for the treatment of pediatric meningitis has excellent
in vitro activity against L monocytogenes It may prove to be useful for listeria infections but
has not yet been approved for this indication Other antibiotics are less effective against L
monocytogenes
The usual duration of therapy for Listeria meningitis is 14 to 21 days
Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus
agalactiae) meningitis is discussed separately (See Group B streptococcal infection in
neonates and young infants section on Treatment)
S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is
nafcillin or oxacillin [1837]
Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or
Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)
The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin
[183738]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some
experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses
(maximum dose 600 mgday) to vancomycin either orally or by intravenous
administration
Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses or
Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day
maximum dose 1200 mgday
Inflammation of the meninges does not appear to affect penetration of linezolid into
the CSF [39-42] Rapid penetration has been demonstrated in children and
adolescents [42] However CSF concentrations are variable and correlation of CSF
and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some
case reports document successful linezolid treatment of staphylococcal meningitis
[3743]
Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated
with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside
often can be discontinued after the first week once the CSF cultures have been documented
to be sterile Consultation with an expert in pediatric infectious diseases is recommended for
children with meningitis caused by a Gram-negative rod One suggested regimen is as
follows
Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided
doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
Antibiotic regimen mdash There are two general principles of antibiotic therapy for bacterial
meningitis [4]
The agent(s) used must be bactericidal against the infecting organism
The agent(s) used must be able to penetrate past the blood-brain barrier to reach a
sufficient concentration in the CSF
Bactericidal agents mdash Since the CSF is a site of impaired humoral immunity a fundamental
principle of therapy of bacterial meningitis is that antibiotics must achieve a bactericidal effect
within CSF to result in optimal microbiologic cure [56] This principle is supported by clinical
observations of poor outcomes in patients receiving bacteriostatic therapy (eg clindamycin
tetracycline) [7] as well as direct experimental evidence in which bactericidal antibiotic
therapy resulted in optimal microbiologic cure and survival in animals with pneumococcal
meningitis [8]
Chloramphenicol is a bacteriostatic drug for most enteric Gram-negative rods however it
usually is bactericidal for Haemophilus influenzae Neisseria meningitidis and Streptococcus
pneumoniae and has been used extensively and successfully to treat meningitis caused by
these organisms
Drug entry into CSF mdash Treatment of bacterial meningitis requires adequate concentration of
antibiotics in the CSF Most drugs reach peak concentrations in the CSF that are only 10 to
20 percent of peak concentrations in the serum This is because the blood-brain barrier
blocks macromolecule entry into the CSF with small lipophilic molecules penetrating most
easily
The peak concentration of drugs in CSF increases with inflammation of the blood-brain
barrier This was illustrated in one study that sequentially monitored CSF and serum penicillin
levels in children with bacterial meningitis The mean CSFserum ratio two hours after
administration of the same intravenous dose of penicillin was 42 percent on the first day of
therapy but fell to less than 10 percent on the 10th day when the inflammatory changes had
subsided [9] (See Cerebrospinal fluid Physiology and utility of an examination in disease
states section on Blood-brain barrier)
Because of the general limitation in antibiotic penetration into the CSF all patients should be
treated with intravenous antibiotics Oral antibiotics should be avoided since the dose and
tissue levels tend to be considerably lower than with parenteral agents One exception can be
made for chloramphenicol which has been administered successfully by the oral route to
treat H influenzae type b (Hib) meningitis in children [10]
Choice of regimen mdash The choice of regimen depends upon whether the pathogen is known
since regimens for empiric therapy pose a different set of management issues than do those
used to treat known pathogens (See Empiric therapy below and Specific therapy below)
PRETREATMENT EVALUATION mdash If possible the pretreatment evaluation of children with
suspected bacterial meningitis should include a complete history and physical examination
cerebrospinal fluid (CSF) examination (cell count and differential glucose protein Gram stain
and culture) complete blood count (CBC) with differential and platelet count two aerobic
blood cultures serum electrolytes glucose blood urea nitrogen and creatinine evaluation of
clotting function is especially indicated if petechiae or purpuric lesions are noted (algorithm 1)
In cases in which the performance of a lumbar puncture (LP) is delayed by rapidly
deteriorating clinical status or the need for neuroimaging blood cultures should be obtained
before the administration of antibiotic therapy (algorithm 1)
The pretreatment evaluation of infants and children with suspected bacterial meningitis is
discussed in greater detail separately (See Clinical features and diagnosis of acute bacterial
meningitis in children older than one month of age section on Evaluation)
IMMEDIATE MANAGEMENT mdash Immediate management of children with suspected bacterial
meningitis includes [11]
Assurance of adequate ventilation and cardiac perfusion (see Initial assessment and
stabilization of children with respiratory or circulatory compromise)
Initiation of hemodynamic monitoring and support at the same time as obtaining
appropriate laboratory studies (blood and cerebrospinal fluid [CSF]) (see
Pretreatment evaluation above)
Establishment of venous access (see Vascular (venous) access for pediatric
resuscitation and other pediatric emergencies)
Administration of fluids as necessary to treat septic shock if present (see Systemic
inflammatory response syndrome (SIRS) and sepsis in children Definitions
epidemiology clinical manifestations and diagnosis)
Administration of dexamethasone if warranted after assessment of potential benefits
and risks before or immediately after the first dose of antimicrobial therapy (see
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
Administration of the first dose of empiric antibiotics (vancomycin [15 mgkg] plus
either cefotaxime [100 mgkg] or ceftriaxone [50 mgkg]) (see Empiric regimen
below)
Administration of glucose (025 gkg) for documented hypoglycemia (serum glucose
concentration less than 40 mgdL [22 mmolL]) (see Approach to hypoglycemia in
infants and children section on Glucose therapy)
Treatment of acidosis and coagulopathy if present (see Systemic inflammatory
response syndrome (SIRS) and sepsis in children Definitions epidemiology clinical
manifestations and diagnosis and Disseminated intravascular coagulation in infants
and children)
SUPPORTIVE CARE
Fluid management mdash Careful management of fluid and electrolyte balance is an important
aspect of supportive therapy Both over- and under-hydration are associated with adverse
outcomes [12]
Children who are in shock should receive sufficient quantities of isotonic fluid to maintain
blood pressure and cerebral perfusion [13] The management of septic shock in children is
discussed separately (See Systemic inflammatory response syndrome (SIRS) and sepsis in
children Definitions epidemiology clinical manifestations and diagnosis)
Children who are hypovolemic but not in shock should be rehydrated with careful and
frequent attention to fluid status Body weight urine volume and specific gravity and serum
electrolytes should be monitored regularly (See Treatment of hypovolemia (dehydration) in
children)
For children who are neither in shock nor hypovolemic we suggest moderate fluid restriction
(1200 mLm2 per day) initially especially if the serum sodium is less than 130 mEqL until
evidence of inappropriate secretion of antidiuretic hormone can be excluded Body weight
urine volume and specific gravity serum electrolytes and if indicated serum and urine
osmolalities should be carefully monitored Fluid administration can be liberalized gradually
as the serum sodium reaches 135 mEqL Most children can receive maintenance fluid intake
within 24 hours of hospitalization
Monitoring mdash Children who are being treated for bacterial meningitis should be monitored
carefully for complications (eg increased intracranial pressure seizure activity development
of infected subdural effusions) particularly during the first two to three days of treatment
when complications are most likely to occur [13-15]
Heart rate blood pressure and respiratory rate should be monitored regularly with a
frequency appropriate to the care setting
A complete neurologic examination should be performed daily rapid assessment of
neurologic function should be performed several times per day for the first several
days of treatment
Head circumference should be measured daily in children younger than 18 months
EMPIRIC THERAPY mdash The organism causing bacterial meningitis seldom is known at the
outset of therapy as a result an empiric treatment plan usually needs to be formulated An
awareness of the most likely pathogens knowledge of local susceptibility patterns and
assessment of the degree of urgency are necessary to devise an optimal empiric treatment
strategy Once culture results are available treatment should be modified to follow the
guidelines for specific pathogens (See Specific therapy below)
Major pathogens mdash The two most common causes of bacterial meningitis in infants and
children who have received a full series of H influenzae type b (Hib) and pneumococcal
conjugate vaccines are S pneumoniae and N meningitidis [16] Among S pneumoniae
isolates antibiotic resistance remains a concern In developing countries that do not routinely
immunize against Hib Hib continues to be a frequent cause of meningitis [17] (See Clinical
features and diagnosis of acute bacterial meningitis in children older than one month of age
section on Epidemiology)
Group B streptococcus Escherichia coli and Listeria monocytogenes are important causes in
infants younger than three months (See Clinical features and diagnosis of acute bacterial
meningitis in children older than one month of age section on Epidemiology and Clinical
features and diagnosis of bacterial meningitis in the neonate section on Etiology)
Empiric regimen mdash The empiric regimen should include coverage for penicillin-resistant S
pneumoniae and N meningitidis the two most common causes of bacterial meningitis in
infants and children Additional coverage for other organisms may be indicated in children
with immune deficiency recent neurosurgery penetrating head trauma and anatomic
defects The cerebrospinal fluid (CSF) Gram stain may provide important clues for the need to
add additional antibiotics to cover for more unusual organisms Broad-spectrum antimicrobial
therapy should be continued until CSF culture results are available because Gram stain
results are subject to observer misinterpretation [18] (See Special circumstances below)
An appropriate empiric regimen (ie one that covers antibiotic-resistant S pneumoniae N
meningitidis and Hib) includes high doses of a third-generation cephalosporin (eg
cefotaxime ceftriaxone) and vancomycin [19]
Cefotaxime 300 mgkg per day intravenously (IV) (maximum dose 12 gday) in 3 or 4
divided doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2
divided doses plus
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses
If ceftriaxone is used we suggest twice daily dosing to avoid the possibility of inadequate
treatment in the event of dosing errors delayed doses or missed doses [13] Some experts
suggest the addition of rifampin to the empiric regimen if dexamethasone is administered [18]
(See Pneumococcal meningitis in children section on Empiric therapy)
Consultation with an expert in pediatric infectious diseases is recommended for children in
whom cephalosporins or vancomycin are contraindicated
Use of dexamethasone mdash Issues related to neurologic sequelae after bacterial meningitis
and the possible role of dexamethasone therapy to minimize these complications are
discussed separately (See Neurologic complications of bacterial meningitis in children and
Dexamethasone and other measures to prevent neurologic complications of bacterial
meningitis in children section on Dexamethasone)
The decision to use dexamethasone in children with suspected bacterial meningitis must be
individualized Factors to be weighed in this decision include
The etiologic agent
The ability to administer dexamethasone before or within 1 hour of the first dose of
antibiotic therapy
The empiric antibiotic regimen
The potential adverse effects
The American Academy of Pediatrics (AAP) Committee on Infectious Diseases suggests that
dexamethasone therapy may be beneficial in children with Hib meningitis if given before or at
the same time as the first dose of antimicrobial therapy [20] The AAP Committee on
Infectious Diseases suggests that dexamethasone therapy be considered for infants and
children older than six weeks with pneumococcal meningitis after weighing the potential risks
and benefits [21]
In accordance with the AAP Committee on Infectious Diseases we recommend adjunctive
therapy with dexamethasone for children with Hib meningitis We suggest that decisions
regarding the use of dexamethasone in children with pneumococcal meningitis or in those in
whom bacterial meningitis is suspected but the etiology unknown be individualized
depending upon careful analysis of the potential risks and benefits The author of this topic
review usually does not administer dexamethasone to children with suspected pneumococcal
or meningococcal meningitis In the same patients other experts may choose to use
dexamethasone (See Pneumococcal meningitis in children section on Dexamethasone)
Regimen mdash If the decision is made to use dexamethasone dexamethasone should be given
before or concurrently with the first dose of the antimicrobial agent(s) it is probably of no
benefit if given more than 1 hour later [18] The regimen for dexamethasone is
Dexamethasone 015 mgkg per dose every 6 hours for 2 to 4 days [13] Two days of
dexamethasone appear to be as effective as and less toxic than longer courses [22]
Special circumstances mdash The treatment of bacterial meningitis in children with immune
deficiency recent neurosurgery anatomic defects penetrating head trauma CSF leak and
during epidemics requires consultation with an expert in pediatric infectious diseases
Immune deficiency mdash Vancomycin plus either cefotaxime or ceftriaxone given as described
above are reasonable empiric coverage for most children with an underlying defect in host
defense (See Empiric regimen above)
If a Gram-negative rod is observed on Gram stain of the CSF the addition of an
aminoglycoside (eg gentamicin amikacin) to these two agents is recommended (See Gram-
negative rods below)
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 22 5 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Peak and trough serum concentrations must be monitored when aminoglycosides are used
[23]
Cancer and neutropenia mdash In a retrospective case series of 40 cases of bacterial or fungal
meningitis in 36 neutropenic pediatric cancer patients (two-thirds of whom had recent
neurosurgery a central nervous system [CNS] device or CSF leak) S pneumoniae and
Staphylococcus aureus were the two most common isolates [24] Empiric therapy in such
patients should be based upon the Gram stain results Initial therapy typically includes
vancomycin plus an aminoglycoside plus either cefotaxime or ceftriaxone If there is any
concern about Pseudomonas aeruginosa or an increased risk for infection caused by an
extended-spectrum beta-lactamase (ESBL)-producing organism meropenem may be
warranted as an alternative to cefotaxime or ceftriaxone
T cell defects mdash S pneumoniae and L monocytogenes are the most likely causes of
bacterial meningitis in patients with defective cell-mediated immunity [25] To address these
pathogens the empiric regimen for children with defects in T cell immunity should include
vancomycin plus either cefotaxime or ceftriaxone dosed as recommended above and high-
dose ampicillin (see Empiric regimen above) The dose of ampicillin is as follows
Ampicillin 300 to 400 mgkg IV per day (maximum dose 10 to 12 gday) in 4 or 6
divided doses
Recent neurosurgery mdash In addition to the usual nosocomial pathogens that may complicate
any surgical procedure coagulase-negative staphylococci (such as Staphylococcus
epidermidis) and S aureus are important causes of meningitis in patients who have had
recent neurosurgery Patients who undergo operations that involve a prosthetic device such
as a ventricular shunt or drain are clearly at risk for developing infection (See Infections of
central nervous system shunts and other devices)
Patients who have undergone recent neurosurgery also are at increased risk for meningitis
with enteric Gram-negative rods such as E coli and Klebsiella species as well as P
aeruginosa (See Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in this setting usually consists of a combination of a third-generation
cephalosporin and vancomycin In addition an aminoglycoside (eg gentamicin amikacin)
should be added if Gram-negative bacilli are noted on CSF Gram stain
Alternative regimens include
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
The local antibiogram can help to guide which of the agents directed against Gram-
negative organisms might be most appropriate (eg a high rate of resistance to
ceftazidime suggests meropenem is a better choice)
Recent placement of CSF shunt mdash In infants and children who have had recent placement
of a CSF shunt vancomycin plus either cefotaxime or ceftriaxone are recommended [18]
Anatomic defects mdash Children with anatomic defects (eg dermal sinus (picture 1) urinary
tract anomalies) are at increased risk for meningitis with S aureus or coagulase-negative
staphylococcus and enteric Gram-negative rods such as E coli and Klebsiella (See
Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in children with anatomic defects should include vancomycin plus either
cefotaxime or ceftriaxone dosed as recommended above (See Empiric regimen above)
In addition an aminoglycoside (eg gentamicin amikacin) should be added if Gram-negative
bacilli are noted on CSF Gram stain
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 225 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Penetrating head trauma mdash Patients with penetrating head trauma are at risk for meningitis
with S aureus coagulase-negative staphylococci (such as S epidermidis) and aerobic
Gram-negative bacilli including P aeruginosa [18]
Empiric therapy in this setting usually consists of a combination of vancomycin plus an
extended-spectrum cephalosporin (cefepime or ceftazidime) or meropenem plus an
aminoglycoside [18]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
plus
Gentamicin 75 mgkg per day IV in 3 divided doses or amikacin 15 to 225 mgkg per
day IV (maximum dose 15 gday) in 3 divided doses
CSF leak mdash Patients with a CSF leak (CSF rhinorrhea or otorrhea) should be treated for
presumed pneumococcal meningitis since S pneumoniae is the most likely organism in this
setting Pneumococcal meningitis in these patients is usually less severe than that caused by
hematogenous invasion and the prognosis is somewhat better Nevertheless because of the
possibility of an isolate highly resistant to penicillin such patients should be treated with a
third-generation cephalosporin plus vancomycin until culture results return This regimen
also will cover H influenzae which rarely causes meningitis in patients with dural defects
(See Empiric regimen above)
Epidemics mdash The empiric treatment of bacterial meningitis during epidemics in which N
meningitidis is suspected is discussed separately (See Treatment and prevention of
meningococcal infection)
SPECIFIC THERAPY mdash Once the causative agent and its in vitro antimicrobial susceptibility
pattern are known empiric antimicrobial therapy can be altered accordingly
S pneumoniae mdash The treatment of pneumococcal meningitis is discussed in detail
separately (See Pneumococcal meningitis in children section on Overview of treatment)
Therapeutic options for pneumococcal meningitis according to antibiotic susceptibility profiles
are outlined in the table (table 1) The usual duration of therapy in uncomplicated cases of S
pneumoniae meningitis is 10 to 14 days
N meningitidis mdash Meningococcal meningitis is best treated with penicillin
Penicillin G 250000 to 300000 Ukg per day IV (maximum 24 million Uday) in 4 or 6
divided doses
A third-generation cephalosporin is an effective alternative to penicillin for children with
penicillin allergy that is not characterized by anaphylaxis [2627] (See Allergy to penicillins
and Penicillin-allergic patients Use of cephalosporins carbapenems and monobactams)
Possible regimens include
Cefotaxime 225 to 300 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided
doses or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
For patients with penicillin allergy characterized by anaphylaxis chloramphenicol is a
recommended alternative [27] Desensitizing the patient to the third-generation cephalosporin
is another option
Chloramphenicol 75 to 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4
divided doses
Although scattered cases of N meningitidis resistant to penicillin have been reported such
strains are rare Relative resistance to penicillin occurs more commonly but does not have an
impact on the response to penicillin or cephalosporin therapy [2829] (See Treatment and
prevention of meningococcal infection section on Penicillin)
A five- to seven-day duration of therapy is adequate for meningococcal meningitis and
eradication of the organism from the cerebrospinal fluid (CSF) [27] However neither penicillin
nor chloramphenicol therapy reliably eradicates nasopharyngeal carriage of N meningitidis
Patients treated with penicillin or chloramphenicol should receive antimicrobial therapy to
eradicate nasopharyngeal carriage before hospital discharge to prevent transmission of the
organism to contacts (See Treatment and prevention of meningococcal infection section on
Antimicrobial chemoprophylaxis)
H influenzae type b mdash Ceftriaxone or cefotaxime is the treatment of choice for ampicillin-
resistant H influenzae type b (Hib) meningitis [2030-32]
Cefotaxime 200 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided doses
or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
Ampicillin is effective for susceptible strains
Ampicillin 300 to 400 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6
divided doses
For patients with penicillin allergy characterized by anaphylaxis desensitizing the patient is
one option Chloramphenicol is another
Chloramphenicol 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4 divided
doses
Cefuroxime should not be used to treat Hib meningitis because it is associated with less
rapid sterilization of the CSF and a greater incidence of hearing loss [3031]
Patients with Hib meningitis should be treated for 7 to 10 days Pharyngeal colonization
persists after curative therapy with agents other than ceftriaxone and cefotaxime Patients
who are not treated with ceftriaxone or cefotaxime should receive rifampin before hospital
discharge to prevent transmission of the organism to contacts For patients who are treated
with chloramphenicol rifampin therapy should be delayed until chloramphenicol is
discontinued since concomitant administration of rifampin may reduce serum concentrations
of chloramphenicol [33] (See Prevention of Haemophilus influenzae infection section on
Antibiotic prophylaxis of close contacts)
L monocytogenes mdash L meningitis traditionally has been treated with ampicillin and
gentamicin because resistance to these drugs is quite rare [34] Although gentamicin has
poor CSF penetration it is used for synergy [35]
Ampicillin 300 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative for penicillin-allergic patients
[36] The dose for TMP-SMX is as follows
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses
Meropenem a carbapenem approved for the treatment of pediatric meningitis has excellent
in vitro activity against L monocytogenes It may prove to be useful for listeria infections but
has not yet been approved for this indication Other antibiotics are less effective against L
monocytogenes
The usual duration of therapy for Listeria meningitis is 14 to 21 days
Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus
agalactiae) meningitis is discussed separately (See Group B streptococcal infection in
neonates and young infants section on Treatment)
S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is
nafcillin or oxacillin [1837]
Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or
Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)
The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin
[183738]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some
experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses
(maximum dose 600 mgday) to vancomycin either orally or by intravenous
administration
Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses or
Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day
maximum dose 1200 mgday
Inflammation of the meninges does not appear to affect penetration of linezolid into
the CSF [39-42] Rapid penetration has been demonstrated in children and
adolescents [42] However CSF concentrations are variable and correlation of CSF
and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some
case reports document successful linezolid treatment of staphylococcal meningitis
[3743]
Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated
with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside
often can be discontinued after the first week once the CSF cultures have been documented
to be sterile Consultation with an expert in pediatric infectious diseases is recommended for
children with meningitis caused by a Gram-negative rod One suggested regimen is as
follows
Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided
doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
and culture) complete blood count (CBC) with differential and platelet count two aerobic
blood cultures serum electrolytes glucose blood urea nitrogen and creatinine evaluation of
clotting function is especially indicated if petechiae or purpuric lesions are noted (algorithm 1)
In cases in which the performance of a lumbar puncture (LP) is delayed by rapidly
deteriorating clinical status or the need for neuroimaging blood cultures should be obtained
before the administration of antibiotic therapy (algorithm 1)
The pretreatment evaluation of infants and children with suspected bacterial meningitis is
discussed in greater detail separately (See Clinical features and diagnosis of acute bacterial
meningitis in children older than one month of age section on Evaluation)
IMMEDIATE MANAGEMENT mdash Immediate management of children with suspected bacterial
meningitis includes [11]
Assurance of adequate ventilation and cardiac perfusion (see Initial assessment and
stabilization of children with respiratory or circulatory compromise)
Initiation of hemodynamic monitoring and support at the same time as obtaining
appropriate laboratory studies (blood and cerebrospinal fluid [CSF]) (see
Pretreatment evaluation above)
Establishment of venous access (see Vascular (venous) access for pediatric
resuscitation and other pediatric emergencies)
Administration of fluids as necessary to treat septic shock if present (see Systemic
inflammatory response syndrome (SIRS) and sepsis in children Definitions
epidemiology clinical manifestations and diagnosis)
Administration of dexamethasone if warranted after assessment of potential benefits
and risks before or immediately after the first dose of antimicrobial therapy (see
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
Administration of the first dose of empiric antibiotics (vancomycin [15 mgkg] plus
either cefotaxime [100 mgkg] or ceftriaxone [50 mgkg]) (see Empiric regimen
below)
Administration of glucose (025 gkg) for documented hypoglycemia (serum glucose
concentration less than 40 mgdL [22 mmolL]) (see Approach to hypoglycemia in
infants and children section on Glucose therapy)
Treatment of acidosis and coagulopathy if present (see Systemic inflammatory
response syndrome (SIRS) and sepsis in children Definitions epidemiology clinical
manifestations and diagnosis and Disseminated intravascular coagulation in infants
and children)
SUPPORTIVE CARE
Fluid management mdash Careful management of fluid and electrolyte balance is an important
aspect of supportive therapy Both over- and under-hydration are associated with adverse
outcomes [12]
Children who are in shock should receive sufficient quantities of isotonic fluid to maintain
blood pressure and cerebral perfusion [13] The management of septic shock in children is
discussed separately (See Systemic inflammatory response syndrome (SIRS) and sepsis in
children Definitions epidemiology clinical manifestations and diagnosis)
Children who are hypovolemic but not in shock should be rehydrated with careful and
frequent attention to fluid status Body weight urine volume and specific gravity and serum
electrolytes should be monitored regularly (See Treatment of hypovolemia (dehydration) in
children)
For children who are neither in shock nor hypovolemic we suggest moderate fluid restriction
(1200 mLm2 per day) initially especially if the serum sodium is less than 130 mEqL until
evidence of inappropriate secretion of antidiuretic hormone can be excluded Body weight
urine volume and specific gravity serum electrolytes and if indicated serum and urine
osmolalities should be carefully monitored Fluid administration can be liberalized gradually
as the serum sodium reaches 135 mEqL Most children can receive maintenance fluid intake
within 24 hours of hospitalization
Monitoring mdash Children who are being treated for bacterial meningitis should be monitored
carefully for complications (eg increased intracranial pressure seizure activity development
of infected subdural effusions) particularly during the first two to three days of treatment
when complications are most likely to occur [13-15]
Heart rate blood pressure and respiratory rate should be monitored regularly with a
frequency appropriate to the care setting
A complete neurologic examination should be performed daily rapid assessment of
neurologic function should be performed several times per day for the first several
days of treatment
Head circumference should be measured daily in children younger than 18 months
EMPIRIC THERAPY mdash The organism causing bacterial meningitis seldom is known at the
outset of therapy as a result an empiric treatment plan usually needs to be formulated An
awareness of the most likely pathogens knowledge of local susceptibility patterns and
assessment of the degree of urgency are necessary to devise an optimal empiric treatment
strategy Once culture results are available treatment should be modified to follow the
guidelines for specific pathogens (See Specific therapy below)
Major pathogens mdash The two most common causes of bacterial meningitis in infants and
children who have received a full series of H influenzae type b (Hib) and pneumococcal
conjugate vaccines are S pneumoniae and N meningitidis [16] Among S pneumoniae
isolates antibiotic resistance remains a concern In developing countries that do not routinely
immunize against Hib Hib continues to be a frequent cause of meningitis [17] (See Clinical
features and diagnosis of acute bacterial meningitis in children older than one month of age
section on Epidemiology)
Group B streptococcus Escherichia coli and Listeria monocytogenes are important causes in
infants younger than three months (See Clinical features and diagnosis of acute bacterial
meningitis in children older than one month of age section on Epidemiology and Clinical
features and diagnosis of bacterial meningitis in the neonate section on Etiology)
Empiric regimen mdash The empiric regimen should include coverage for penicillin-resistant S
pneumoniae and N meningitidis the two most common causes of bacterial meningitis in
infants and children Additional coverage for other organisms may be indicated in children
with immune deficiency recent neurosurgery penetrating head trauma and anatomic
defects The cerebrospinal fluid (CSF) Gram stain may provide important clues for the need to
add additional antibiotics to cover for more unusual organisms Broad-spectrum antimicrobial
therapy should be continued until CSF culture results are available because Gram stain
results are subject to observer misinterpretation [18] (See Special circumstances below)
An appropriate empiric regimen (ie one that covers antibiotic-resistant S pneumoniae N
meningitidis and Hib) includes high doses of a third-generation cephalosporin (eg
cefotaxime ceftriaxone) and vancomycin [19]
Cefotaxime 300 mgkg per day intravenously (IV) (maximum dose 12 gday) in 3 or 4
divided doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2
divided doses plus
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses
If ceftriaxone is used we suggest twice daily dosing to avoid the possibility of inadequate
treatment in the event of dosing errors delayed doses or missed doses [13] Some experts
suggest the addition of rifampin to the empiric regimen if dexamethasone is administered [18]
(See Pneumococcal meningitis in children section on Empiric therapy)
Consultation with an expert in pediatric infectious diseases is recommended for children in
whom cephalosporins or vancomycin are contraindicated
Use of dexamethasone mdash Issues related to neurologic sequelae after bacterial meningitis
and the possible role of dexamethasone therapy to minimize these complications are
discussed separately (See Neurologic complications of bacterial meningitis in children and
Dexamethasone and other measures to prevent neurologic complications of bacterial
meningitis in children section on Dexamethasone)
The decision to use dexamethasone in children with suspected bacterial meningitis must be
individualized Factors to be weighed in this decision include
The etiologic agent
The ability to administer dexamethasone before or within 1 hour of the first dose of
antibiotic therapy
The empiric antibiotic regimen
The potential adverse effects
The American Academy of Pediatrics (AAP) Committee on Infectious Diseases suggests that
dexamethasone therapy may be beneficial in children with Hib meningitis if given before or at
the same time as the first dose of antimicrobial therapy [20] The AAP Committee on
Infectious Diseases suggests that dexamethasone therapy be considered for infants and
children older than six weeks with pneumococcal meningitis after weighing the potential risks
and benefits [21]
In accordance with the AAP Committee on Infectious Diseases we recommend adjunctive
therapy with dexamethasone for children with Hib meningitis We suggest that decisions
regarding the use of dexamethasone in children with pneumococcal meningitis or in those in
whom bacterial meningitis is suspected but the etiology unknown be individualized
depending upon careful analysis of the potential risks and benefits The author of this topic
review usually does not administer dexamethasone to children with suspected pneumococcal
or meningococcal meningitis In the same patients other experts may choose to use
dexamethasone (See Pneumococcal meningitis in children section on Dexamethasone)
Regimen mdash If the decision is made to use dexamethasone dexamethasone should be given
before or concurrently with the first dose of the antimicrobial agent(s) it is probably of no
benefit if given more than 1 hour later [18] The regimen for dexamethasone is
Dexamethasone 015 mgkg per dose every 6 hours for 2 to 4 days [13] Two days of
dexamethasone appear to be as effective as and less toxic than longer courses [22]
Special circumstances mdash The treatment of bacterial meningitis in children with immune
deficiency recent neurosurgery anatomic defects penetrating head trauma CSF leak and
during epidemics requires consultation with an expert in pediatric infectious diseases
Immune deficiency mdash Vancomycin plus either cefotaxime or ceftriaxone given as described
above are reasonable empiric coverage for most children with an underlying defect in host
defense (See Empiric regimen above)
If a Gram-negative rod is observed on Gram stain of the CSF the addition of an
aminoglycoside (eg gentamicin amikacin) to these two agents is recommended (See Gram-
negative rods below)
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 22 5 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Peak and trough serum concentrations must be monitored when aminoglycosides are used
[23]
Cancer and neutropenia mdash In a retrospective case series of 40 cases of bacterial or fungal
meningitis in 36 neutropenic pediatric cancer patients (two-thirds of whom had recent
neurosurgery a central nervous system [CNS] device or CSF leak) S pneumoniae and
Staphylococcus aureus were the two most common isolates [24] Empiric therapy in such
patients should be based upon the Gram stain results Initial therapy typically includes
vancomycin plus an aminoglycoside plus either cefotaxime or ceftriaxone If there is any
concern about Pseudomonas aeruginosa or an increased risk for infection caused by an
extended-spectrum beta-lactamase (ESBL)-producing organism meropenem may be
warranted as an alternative to cefotaxime or ceftriaxone
T cell defects mdash S pneumoniae and L monocytogenes are the most likely causes of
bacterial meningitis in patients with defective cell-mediated immunity [25] To address these
pathogens the empiric regimen for children with defects in T cell immunity should include
vancomycin plus either cefotaxime or ceftriaxone dosed as recommended above and high-
dose ampicillin (see Empiric regimen above) The dose of ampicillin is as follows
Ampicillin 300 to 400 mgkg IV per day (maximum dose 10 to 12 gday) in 4 or 6
divided doses
Recent neurosurgery mdash In addition to the usual nosocomial pathogens that may complicate
any surgical procedure coagulase-negative staphylococci (such as Staphylococcus
epidermidis) and S aureus are important causes of meningitis in patients who have had
recent neurosurgery Patients who undergo operations that involve a prosthetic device such
as a ventricular shunt or drain are clearly at risk for developing infection (See Infections of
central nervous system shunts and other devices)
Patients who have undergone recent neurosurgery also are at increased risk for meningitis
with enteric Gram-negative rods such as E coli and Klebsiella species as well as P
aeruginosa (See Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in this setting usually consists of a combination of a third-generation
cephalosporin and vancomycin In addition an aminoglycoside (eg gentamicin amikacin)
should be added if Gram-negative bacilli are noted on CSF Gram stain
Alternative regimens include
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
The local antibiogram can help to guide which of the agents directed against Gram-
negative organisms might be most appropriate (eg a high rate of resistance to
ceftazidime suggests meropenem is a better choice)
Recent placement of CSF shunt mdash In infants and children who have had recent placement
of a CSF shunt vancomycin plus either cefotaxime or ceftriaxone are recommended [18]
Anatomic defects mdash Children with anatomic defects (eg dermal sinus (picture 1) urinary
tract anomalies) are at increased risk for meningitis with S aureus or coagulase-negative
staphylococcus and enteric Gram-negative rods such as E coli and Klebsiella (See
Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in children with anatomic defects should include vancomycin plus either
cefotaxime or ceftriaxone dosed as recommended above (See Empiric regimen above)
In addition an aminoglycoside (eg gentamicin amikacin) should be added if Gram-negative
bacilli are noted on CSF Gram stain
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 225 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Penetrating head trauma mdash Patients with penetrating head trauma are at risk for meningitis
with S aureus coagulase-negative staphylococci (such as S epidermidis) and aerobic
Gram-negative bacilli including P aeruginosa [18]
Empiric therapy in this setting usually consists of a combination of vancomycin plus an
extended-spectrum cephalosporin (cefepime or ceftazidime) or meropenem plus an
aminoglycoside [18]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
plus
Gentamicin 75 mgkg per day IV in 3 divided doses or amikacin 15 to 225 mgkg per
day IV (maximum dose 15 gday) in 3 divided doses
CSF leak mdash Patients with a CSF leak (CSF rhinorrhea or otorrhea) should be treated for
presumed pneumococcal meningitis since S pneumoniae is the most likely organism in this
setting Pneumococcal meningitis in these patients is usually less severe than that caused by
hematogenous invasion and the prognosis is somewhat better Nevertheless because of the
possibility of an isolate highly resistant to penicillin such patients should be treated with a
third-generation cephalosporin plus vancomycin until culture results return This regimen
also will cover H influenzae which rarely causes meningitis in patients with dural defects
(See Empiric regimen above)
Epidemics mdash The empiric treatment of bacterial meningitis during epidemics in which N
meningitidis is suspected is discussed separately (See Treatment and prevention of
meningococcal infection)
SPECIFIC THERAPY mdash Once the causative agent and its in vitro antimicrobial susceptibility
pattern are known empiric antimicrobial therapy can be altered accordingly
S pneumoniae mdash The treatment of pneumococcal meningitis is discussed in detail
separately (See Pneumococcal meningitis in children section on Overview of treatment)
Therapeutic options for pneumococcal meningitis according to antibiotic susceptibility profiles
are outlined in the table (table 1) The usual duration of therapy in uncomplicated cases of S
pneumoniae meningitis is 10 to 14 days
N meningitidis mdash Meningococcal meningitis is best treated with penicillin
Penicillin G 250000 to 300000 Ukg per day IV (maximum 24 million Uday) in 4 or 6
divided doses
A third-generation cephalosporin is an effective alternative to penicillin for children with
penicillin allergy that is not characterized by anaphylaxis [2627] (See Allergy to penicillins
and Penicillin-allergic patients Use of cephalosporins carbapenems and monobactams)
Possible regimens include
Cefotaxime 225 to 300 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided
doses or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
For patients with penicillin allergy characterized by anaphylaxis chloramphenicol is a
recommended alternative [27] Desensitizing the patient to the third-generation cephalosporin
is another option
Chloramphenicol 75 to 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4
divided doses
Although scattered cases of N meningitidis resistant to penicillin have been reported such
strains are rare Relative resistance to penicillin occurs more commonly but does not have an
impact on the response to penicillin or cephalosporin therapy [2829] (See Treatment and
prevention of meningococcal infection section on Penicillin)
A five- to seven-day duration of therapy is adequate for meningococcal meningitis and
eradication of the organism from the cerebrospinal fluid (CSF) [27] However neither penicillin
nor chloramphenicol therapy reliably eradicates nasopharyngeal carriage of N meningitidis
Patients treated with penicillin or chloramphenicol should receive antimicrobial therapy to
eradicate nasopharyngeal carriage before hospital discharge to prevent transmission of the
organism to contacts (See Treatment and prevention of meningococcal infection section on
Antimicrobial chemoprophylaxis)
H influenzae type b mdash Ceftriaxone or cefotaxime is the treatment of choice for ampicillin-
resistant H influenzae type b (Hib) meningitis [2030-32]
Cefotaxime 200 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided doses
or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
Ampicillin is effective for susceptible strains
Ampicillin 300 to 400 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6
divided doses
For patients with penicillin allergy characterized by anaphylaxis desensitizing the patient is
one option Chloramphenicol is another
Chloramphenicol 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4 divided
doses
Cefuroxime should not be used to treat Hib meningitis because it is associated with less
rapid sterilization of the CSF and a greater incidence of hearing loss [3031]
Patients with Hib meningitis should be treated for 7 to 10 days Pharyngeal colonization
persists after curative therapy with agents other than ceftriaxone and cefotaxime Patients
who are not treated with ceftriaxone or cefotaxime should receive rifampin before hospital
discharge to prevent transmission of the organism to contacts For patients who are treated
with chloramphenicol rifampin therapy should be delayed until chloramphenicol is
discontinued since concomitant administration of rifampin may reduce serum concentrations
of chloramphenicol [33] (See Prevention of Haemophilus influenzae infection section on
Antibiotic prophylaxis of close contacts)
L monocytogenes mdash L meningitis traditionally has been treated with ampicillin and
gentamicin because resistance to these drugs is quite rare [34] Although gentamicin has
poor CSF penetration it is used for synergy [35]
Ampicillin 300 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative for penicillin-allergic patients
[36] The dose for TMP-SMX is as follows
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses
Meropenem a carbapenem approved for the treatment of pediatric meningitis has excellent
in vitro activity against L monocytogenes It may prove to be useful for listeria infections but
has not yet been approved for this indication Other antibiotics are less effective against L
monocytogenes
The usual duration of therapy for Listeria meningitis is 14 to 21 days
Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus
agalactiae) meningitis is discussed separately (See Group B streptococcal infection in
neonates and young infants section on Treatment)
S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is
nafcillin or oxacillin [1837]
Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or
Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)
The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin
[183738]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some
experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses
(maximum dose 600 mgday) to vancomycin either orally or by intravenous
administration
Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses or
Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day
maximum dose 1200 mgday
Inflammation of the meninges does not appear to affect penetration of linezolid into
the CSF [39-42] Rapid penetration has been demonstrated in children and
adolescents [42] However CSF concentrations are variable and correlation of CSF
and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some
case reports document successful linezolid treatment of staphylococcal meningitis
[3743]
Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated
with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside
often can be discontinued after the first week once the CSF cultures have been documented
to be sterile Consultation with an expert in pediatric infectious diseases is recommended for
children with meningitis caused by a Gram-negative rod One suggested regimen is as
follows
Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided
doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
Children who are in shock should receive sufficient quantities of isotonic fluid to maintain
blood pressure and cerebral perfusion [13] The management of septic shock in children is
discussed separately (See Systemic inflammatory response syndrome (SIRS) and sepsis in
children Definitions epidemiology clinical manifestations and diagnosis)
Children who are hypovolemic but not in shock should be rehydrated with careful and
frequent attention to fluid status Body weight urine volume and specific gravity and serum
electrolytes should be monitored regularly (See Treatment of hypovolemia (dehydration) in
children)
For children who are neither in shock nor hypovolemic we suggest moderate fluid restriction
(1200 mLm2 per day) initially especially if the serum sodium is less than 130 mEqL until
evidence of inappropriate secretion of antidiuretic hormone can be excluded Body weight
urine volume and specific gravity serum electrolytes and if indicated serum and urine
osmolalities should be carefully monitored Fluid administration can be liberalized gradually
as the serum sodium reaches 135 mEqL Most children can receive maintenance fluid intake
within 24 hours of hospitalization
Monitoring mdash Children who are being treated for bacterial meningitis should be monitored
carefully for complications (eg increased intracranial pressure seizure activity development
of infected subdural effusions) particularly during the first two to three days of treatment
when complications are most likely to occur [13-15]
Heart rate blood pressure and respiratory rate should be monitored regularly with a
frequency appropriate to the care setting
A complete neurologic examination should be performed daily rapid assessment of
neurologic function should be performed several times per day for the first several
days of treatment
Head circumference should be measured daily in children younger than 18 months
EMPIRIC THERAPY mdash The organism causing bacterial meningitis seldom is known at the
outset of therapy as a result an empiric treatment plan usually needs to be formulated An
awareness of the most likely pathogens knowledge of local susceptibility patterns and
assessment of the degree of urgency are necessary to devise an optimal empiric treatment
strategy Once culture results are available treatment should be modified to follow the
guidelines for specific pathogens (See Specific therapy below)
Major pathogens mdash The two most common causes of bacterial meningitis in infants and
children who have received a full series of H influenzae type b (Hib) and pneumococcal
conjugate vaccines are S pneumoniae and N meningitidis [16] Among S pneumoniae
isolates antibiotic resistance remains a concern In developing countries that do not routinely
immunize against Hib Hib continues to be a frequent cause of meningitis [17] (See Clinical
features and diagnosis of acute bacterial meningitis in children older than one month of age
section on Epidemiology)
Group B streptococcus Escherichia coli and Listeria monocytogenes are important causes in
infants younger than three months (See Clinical features and diagnosis of acute bacterial
meningitis in children older than one month of age section on Epidemiology and Clinical
features and diagnosis of bacterial meningitis in the neonate section on Etiology)
Empiric regimen mdash The empiric regimen should include coverage for penicillin-resistant S
pneumoniae and N meningitidis the two most common causes of bacterial meningitis in
infants and children Additional coverage for other organisms may be indicated in children
with immune deficiency recent neurosurgery penetrating head trauma and anatomic
defects The cerebrospinal fluid (CSF) Gram stain may provide important clues for the need to
add additional antibiotics to cover for more unusual organisms Broad-spectrum antimicrobial
therapy should be continued until CSF culture results are available because Gram stain
results are subject to observer misinterpretation [18] (See Special circumstances below)
An appropriate empiric regimen (ie one that covers antibiotic-resistant S pneumoniae N
meningitidis and Hib) includes high doses of a third-generation cephalosporin (eg
cefotaxime ceftriaxone) and vancomycin [19]
Cefotaxime 300 mgkg per day intravenously (IV) (maximum dose 12 gday) in 3 or 4
divided doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2
divided doses plus
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses
If ceftriaxone is used we suggest twice daily dosing to avoid the possibility of inadequate
treatment in the event of dosing errors delayed doses or missed doses [13] Some experts
suggest the addition of rifampin to the empiric regimen if dexamethasone is administered [18]
(See Pneumococcal meningitis in children section on Empiric therapy)
Consultation with an expert in pediatric infectious diseases is recommended for children in
whom cephalosporins or vancomycin are contraindicated
Use of dexamethasone mdash Issues related to neurologic sequelae after bacterial meningitis
and the possible role of dexamethasone therapy to minimize these complications are
discussed separately (See Neurologic complications of bacterial meningitis in children and
Dexamethasone and other measures to prevent neurologic complications of bacterial
meningitis in children section on Dexamethasone)
The decision to use dexamethasone in children with suspected bacterial meningitis must be
individualized Factors to be weighed in this decision include
The etiologic agent
The ability to administer dexamethasone before or within 1 hour of the first dose of
antibiotic therapy
The empiric antibiotic regimen
The potential adverse effects
The American Academy of Pediatrics (AAP) Committee on Infectious Diseases suggests that
dexamethasone therapy may be beneficial in children with Hib meningitis if given before or at
the same time as the first dose of antimicrobial therapy [20] The AAP Committee on
Infectious Diseases suggests that dexamethasone therapy be considered for infants and
children older than six weeks with pneumococcal meningitis after weighing the potential risks
and benefits [21]
In accordance with the AAP Committee on Infectious Diseases we recommend adjunctive
therapy with dexamethasone for children with Hib meningitis We suggest that decisions
regarding the use of dexamethasone in children with pneumococcal meningitis or in those in
whom bacterial meningitis is suspected but the etiology unknown be individualized
depending upon careful analysis of the potential risks and benefits The author of this topic
review usually does not administer dexamethasone to children with suspected pneumococcal
or meningococcal meningitis In the same patients other experts may choose to use
dexamethasone (See Pneumococcal meningitis in children section on Dexamethasone)
Regimen mdash If the decision is made to use dexamethasone dexamethasone should be given
before or concurrently with the first dose of the antimicrobial agent(s) it is probably of no
benefit if given more than 1 hour later [18] The regimen for dexamethasone is
Dexamethasone 015 mgkg per dose every 6 hours for 2 to 4 days [13] Two days of
dexamethasone appear to be as effective as and less toxic than longer courses [22]
Special circumstances mdash The treatment of bacterial meningitis in children with immune
deficiency recent neurosurgery anatomic defects penetrating head trauma CSF leak and
during epidemics requires consultation with an expert in pediatric infectious diseases
Immune deficiency mdash Vancomycin plus either cefotaxime or ceftriaxone given as described
above are reasonable empiric coverage for most children with an underlying defect in host
defense (See Empiric regimen above)
If a Gram-negative rod is observed on Gram stain of the CSF the addition of an
aminoglycoside (eg gentamicin amikacin) to these two agents is recommended (See Gram-
negative rods below)
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 22 5 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Peak and trough serum concentrations must be monitored when aminoglycosides are used
[23]
Cancer and neutropenia mdash In a retrospective case series of 40 cases of bacterial or fungal
meningitis in 36 neutropenic pediatric cancer patients (two-thirds of whom had recent
neurosurgery a central nervous system [CNS] device or CSF leak) S pneumoniae and
Staphylococcus aureus were the two most common isolates [24] Empiric therapy in such
patients should be based upon the Gram stain results Initial therapy typically includes
vancomycin plus an aminoglycoside plus either cefotaxime or ceftriaxone If there is any
concern about Pseudomonas aeruginosa or an increased risk for infection caused by an
extended-spectrum beta-lactamase (ESBL)-producing organism meropenem may be
warranted as an alternative to cefotaxime or ceftriaxone
T cell defects mdash S pneumoniae and L monocytogenes are the most likely causes of
bacterial meningitis in patients with defective cell-mediated immunity [25] To address these
pathogens the empiric regimen for children with defects in T cell immunity should include
vancomycin plus either cefotaxime or ceftriaxone dosed as recommended above and high-
dose ampicillin (see Empiric regimen above) The dose of ampicillin is as follows
Ampicillin 300 to 400 mgkg IV per day (maximum dose 10 to 12 gday) in 4 or 6
divided doses
Recent neurosurgery mdash In addition to the usual nosocomial pathogens that may complicate
any surgical procedure coagulase-negative staphylococci (such as Staphylococcus
epidermidis) and S aureus are important causes of meningitis in patients who have had
recent neurosurgery Patients who undergo operations that involve a prosthetic device such
as a ventricular shunt or drain are clearly at risk for developing infection (See Infections of
central nervous system shunts and other devices)
Patients who have undergone recent neurosurgery also are at increased risk for meningitis
with enteric Gram-negative rods such as E coli and Klebsiella species as well as P
aeruginosa (See Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in this setting usually consists of a combination of a third-generation
cephalosporin and vancomycin In addition an aminoglycoside (eg gentamicin amikacin)
should be added if Gram-negative bacilli are noted on CSF Gram stain
Alternative regimens include
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
The local antibiogram can help to guide which of the agents directed against Gram-
negative organisms might be most appropriate (eg a high rate of resistance to
ceftazidime suggests meropenem is a better choice)
Recent placement of CSF shunt mdash In infants and children who have had recent placement
of a CSF shunt vancomycin plus either cefotaxime or ceftriaxone are recommended [18]
Anatomic defects mdash Children with anatomic defects (eg dermal sinus (picture 1) urinary
tract anomalies) are at increased risk for meningitis with S aureus or coagulase-negative
staphylococcus and enteric Gram-negative rods such as E coli and Klebsiella (See
Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in children with anatomic defects should include vancomycin plus either
cefotaxime or ceftriaxone dosed as recommended above (See Empiric regimen above)
In addition an aminoglycoside (eg gentamicin amikacin) should be added if Gram-negative
bacilli are noted on CSF Gram stain
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 225 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Penetrating head trauma mdash Patients with penetrating head trauma are at risk for meningitis
with S aureus coagulase-negative staphylococci (such as S epidermidis) and aerobic
Gram-negative bacilli including P aeruginosa [18]
Empiric therapy in this setting usually consists of a combination of vancomycin plus an
extended-spectrum cephalosporin (cefepime or ceftazidime) or meropenem plus an
aminoglycoside [18]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
plus
Gentamicin 75 mgkg per day IV in 3 divided doses or amikacin 15 to 225 mgkg per
day IV (maximum dose 15 gday) in 3 divided doses
CSF leak mdash Patients with a CSF leak (CSF rhinorrhea or otorrhea) should be treated for
presumed pneumococcal meningitis since S pneumoniae is the most likely organism in this
setting Pneumococcal meningitis in these patients is usually less severe than that caused by
hematogenous invasion and the prognosis is somewhat better Nevertheless because of the
possibility of an isolate highly resistant to penicillin such patients should be treated with a
third-generation cephalosporin plus vancomycin until culture results return This regimen
also will cover H influenzae which rarely causes meningitis in patients with dural defects
(See Empiric regimen above)
Epidemics mdash The empiric treatment of bacterial meningitis during epidemics in which N
meningitidis is suspected is discussed separately (See Treatment and prevention of
meningococcal infection)
SPECIFIC THERAPY mdash Once the causative agent and its in vitro antimicrobial susceptibility
pattern are known empiric antimicrobial therapy can be altered accordingly
S pneumoniae mdash The treatment of pneumococcal meningitis is discussed in detail
separately (See Pneumococcal meningitis in children section on Overview of treatment)
Therapeutic options for pneumococcal meningitis according to antibiotic susceptibility profiles
are outlined in the table (table 1) The usual duration of therapy in uncomplicated cases of S
pneumoniae meningitis is 10 to 14 days
N meningitidis mdash Meningococcal meningitis is best treated with penicillin
Penicillin G 250000 to 300000 Ukg per day IV (maximum 24 million Uday) in 4 or 6
divided doses
A third-generation cephalosporin is an effective alternative to penicillin for children with
penicillin allergy that is not characterized by anaphylaxis [2627] (See Allergy to penicillins
and Penicillin-allergic patients Use of cephalosporins carbapenems and monobactams)
Possible regimens include
Cefotaxime 225 to 300 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided
doses or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
For patients with penicillin allergy characterized by anaphylaxis chloramphenicol is a
recommended alternative [27] Desensitizing the patient to the third-generation cephalosporin
is another option
Chloramphenicol 75 to 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4
divided doses
Although scattered cases of N meningitidis resistant to penicillin have been reported such
strains are rare Relative resistance to penicillin occurs more commonly but does not have an
impact on the response to penicillin or cephalosporin therapy [2829] (See Treatment and
prevention of meningococcal infection section on Penicillin)
A five- to seven-day duration of therapy is adequate for meningococcal meningitis and
eradication of the organism from the cerebrospinal fluid (CSF) [27] However neither penicillin
nor chloramphenicol therapy reliably eradicates nasopharyngeal carriage of N meningitidis
Patients treated with penicillin or chloramphenicol should receive antimicrobial therapy to
eradicate nasopharyngeal carriage before hospital discharge to prevent transmission of the
organism to contacts (See Treatment and prevention of meningococcal infection section on
Antimicrobial chemoprophylaxis)
H influenzae type b mdash Ceftriaxone or cefotaxime is the treatment of choice for ampicillin-
resistant H influenzae type b (Hib) meningitis [2030-32]
Cefotaxime 200 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided doses
or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
Ampicillin is effective for susceptible strains
Ampicillin 300 to 400 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6
divided doses
For patients with penicillin allergy characterized by anaphylaxis desensitizing the patient is
one option Chloramphenicol is another
Chloramphenicol 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4 divided
doses
Cefuroxime should not be used to treat Hib meningitis because it is associated with less
rapid sterilization of the CSF and a greater incidence of hearing loss [3031]
Patients with Hib meningitis should be treated for 7 to 10 days Pharyngeal colonization
persists after curative therapy with agents other than ceftriaxone and cefotaxime Patients
who are not treated with ceftriaxone or cefotaxime should receive rifampin before hospital
discharge to prevent transmission of the organism to contacts For patients who are treated
with chloramphenicol rifampin therapy should be delayed until chloramphenicol is
discontinued since concomitant administration of rifampin may reduce serum concentrations
of chloramphenicol [33] (See Prevention of Haemophilus influenzae infection section on
Antibiotic prophylaxis of close contacts)
L monocytogenes mdash L meningitis traditionally has been treated with ampicillin and
gentamicin because resistance to these drugs is quite rare [34] Although gentamicin has
poor CSF penetration it is used for synergy [35]
Ampicillin 300 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative for penicillin-allergic patients
[36] The dose for TMP-SMX is as follows
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses
Meropenem a carbapenem approved for the treatment of pediatric meningitis has excellent
in vitro activity against L monocytogenes It may prove to be useful for listeria infections but
has not yet been approved for this indication Other antibiotics are less effective against L
monocytogenes
The usual duration of therapy for Listeria meningitis is 14 to 21 days
Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus
agalactiae) meningitis is discussed separately (See Group B streptococcal infection in
neonates and young infants section on Treatment)
S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is
nafcillin or oxacillin [1837]
Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or
Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)
The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin
[183738]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some
experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses
(maximum dose 600 mgday) to vancomycin either orally or by intravenous
administration
Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses or
Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day
maximum dose 1200 mgday
Inflammation of the meninges does not appear to affect penetration of linezolid into
the CSF [39-42] Rapid penetration has been demonstrated in children and
adolescents [42] However CSF concentrations are variable and correlation of CSF
and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some
case reports document successful linezolid treatment of staphylococcal meningitis
[3743]
Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated
with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside
often can be discontinued after the first week once the CSF cultures have been documented
to be sterile Consultation with an expert in pediatric infectious diseases is recommended for
children with meningitis caused by a Gram-negative rod One suggested regimen is as
follows
Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided
doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
Group B streptococcus Escherichia coli and Listeria monocytogenes are important causes in
infants younger than three months (See Clinical features and diagnosis of acute bacterial
meningitis in children older than one month of age section on Epidemiology and Clinical
features and diagnosis of bacterial meningitis in the neonate section on Etiology)
Empiric regimen mdash The empiric regimen should include coverage for penicillin-resistant S
pneumoniae and N meningitidis the two most common causes of bacterial meningitis in
infants and children Additional coverage for other organisms may be indicated in children
with immune deficiency recent neurosurgery penetrating head trauma and anatomic
defects The cerebrospinal fluid (CSF) Gram stain may provide important clues for the need to
add additional antibiotics to cover for more unusual organisms Broad-spectrum antimicrobial
therapy should be continued until CSF culture results are available because Gram stain
results are subject to observer misinterpretation [18] (See Special circumstances below)
An appropriate empiric regimen (ie one that covers antibiotic-resistant S pneumoniae N
meningitidis and Hib) includes high doses of a third-generation cephalosporin (eg
cefotaxime ceftriaxone) and vancomycin [19]
Cefotaxime 300 mgkg per day intravenously (IV) (maximum dose 12 gday) in 3 or 4
divided doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2
divided doses plus
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses
If ceftriaxone is used we suggest twice daily dosing to avoid the possibility of inadequate
treatment in the event of dosing errors delayed doses or missed doses [13] Some experts
suggest the addition of rifampin to the empiric regimen if dexamethasone is administered [18]
(See Pneumococcal meningitis in children section on Empiric therapy)
Consultation with an expert in pediatric infectious diseases is recommended for children in
whom cephalosporins or vancomycin are contraindicated
Use of dexamethasone mdash Issues related to neurologic sequelae after bacterial meningitis
and the possible role of dexamethasone therapy to minimize these complications are
discussed separately (See Neurologic complications of bacterial meningitis in children and
Dexamethasone and other measures to prevent neurologic complications of bacterial
meningitis in children section on Dexamethasone)
The decision to use dexamethasone in children with suspected bacterial meningitis must be
individualized Factors to be weighed in this decision include
The etiologic agent
The ability to administer dexamethasone before or within 1 hour of the first dose of
antibiotic therapy
The empiric antibiotic regimen
The potential adverse effects
The American Academy of Pediatrics (AAP) Committee on Infectious Diseases suggests that
dexamethasone therapy may be beneficial in children with Hib meningitis if given before or at
the same time as the first dose of antimicrobial therapy [20] The AAP Committee on
Infectious Diseases suggests that dexamethasone therapy be considered for infants and
children older than six weeks with pneumococcal meningitis after weighing the potential risks
and benefits [21]
In accordance with the AAP Committee on Infectious Diseases we recommend adjunctive
therapy with dexamethasone for children with Hib meningitis We suggest that decisions
regarding the use of dexamethasone in children with pneumococcal meningitis or in those in
whom bacterial meningitis is suspected but the etiology unknown be individualized
depending upon careful analysis of the potential risks and benefits The author of this topic
review usually does not administer dexamethasone to children with suspected pneumococcal
or meningococcal meningitis In the same patients other experts may choose to use
dexamethasone (See Pneumococcal meningitis in children section on Dexamethasone)
Regimen mdash If the decision is made to use dexamethasone dexamethasone should be given
before or concurrently with the first dose of the antimicrobial agent(s) it is probably of no
benefit if given more than 1 hour later [18] The regimen for dexamethasone is
Dexamethasone 015 mgkg per dose every 6 hours for 2 to 4 days [13] Two days of
dexamethasone appear to be as effective as and less toxic than longer courses [22]
Special circumstances mdash The treatment of bacterial meningitis in children with immune
deficiency recent neurosurgery anatomic defects penetrating head trauma CSF leak and
during epidemics requires consultation with an expert in pediatric infectious diseases
Immune deficiency mdash Vancomycin plus either cefotaxime or ceftriaxone given as described
above are reasonable empiric coverage for most children with an underlying defect in host
defense (See Empiric regimen above)
If a Gram-negative rod is observed on Gram stain of the CSF the addition of an
aminoglycoside (eg gentamicin amikacin) to these two agents is recommended (See Gram-
negative rods below)
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 22 5 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Peak and trough serum concentrations must be monitored when aminoglycosides are used
[23]
Cancer and neutropenia mdash In a retrospective case series of 40 cases of bacterial or fungal
meningitis in 36 neutropenic pediatric cancer patients (two-thirds of whom had recent
neurosurgery a central nervous system [CNS] device or CSF leak) S pneumoniae and
Staphylococcus aureus were the two most common isolates [24] Empiric therapy in such
patients should be based upon the Gram stain results Initial therapy typically includes
vancomycin plus an aminoglycoside plus either cefotaxime or ceftriaxone If there is any
concern about Pseudomonas aeruginosa or an increased risk for infection caused by an
extended-spectrum beta-lactamase (ESBL)-producing organism meropenem may be
warranted as an alternative to cefotaxime or ceftriaxone
T cell defects mdash S pneumoniae and L monocytogenes are the most likely causes of
bacterial meningitis in patients with defective cell-mediated immunity [25] To address these
pathogens the empiric regimen for children with defects in T cell immunity should include
vancomycin plus either cefotaxime or ceftriaxone dosed as recommended above and high-
dose ampicillin (see Empiric regimen above) The dose of ampicillin is as follows
Ampicillin 300 to 400 mgkg IV per day (maximum dose 10 to 12 gday) in 4 or 6
divided doses
Recent neurosurgery mdash In addition to the usual nosocomial pathogens that may complicate
any surgical procedure coagulase-negative staphylococci (such as Staphylococcus
epidermidis) and S aureus are important causes of meningitis in patients who have had
recent neurosurgery Patients who undergo operations that involve a prosthetic device such
as a ventricular shunt or drain are clearly at risk for developing infection (See Infections of
central nervous system shunts and other devices)
Patients who have undergone recent neurosurgery also are at increased risk for meningitis
with enteric Gram-negative rods such as E coli and Klebsiella species as well as P
aeruginosa (See Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in this setting usually consists of a combination of a third-generation
cephalosporin and vancomycin In addition an aminoglycoside (eg gentamicin amikacin)
should be added if Gram-negative bacilli are noted on CSF Gram stain
Alternative regimens include
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
The local antibiogram can help to guide which of the agents directed against Gram-
negative organisms might be most appropriate (eg a high rate of resistance to
ceftazidime suggests meropenem is a better choice)
Recent placement of CSF shunt mdash In infants and children who have had recent placement
of a CSF shunt vancomycin plus either cefotaxime or ceftriaxone are recommended [18]
Anatomic defects mdash Children with anatomic defects (eg dermal sinus (picture 1) urinary
tract anomalies) are at increased risk for meningitis with S aureus or coagulase-negative
staphylococcus and enteric Gram-negative rods such as E coli and Klebsiella (See
Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in children with anatomic defects should include vancomycin plus either
cefotaxime or ceftriaxone dosed as recommended above (See Empiric regimen above)
In addition an aminoglycoside (eg gentamicin amikacin) should be added if Gram-negative
bacilli are noted on CSF Gram stain
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 225 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Penetrating head trauma mdash Patients with penetrating head trauma are at risk for meningitis
with S aureus coagulase-negative staphylococci (such as S epidermidis) and aerobic
Gram-negative bacilli including P aeruginosa [18]
Empiric therapy in this setting usually consists of a combination of vancomycin plus an
extended-spectrum cephalosporin (cefepime or ceftazidime) or meropenem plus an
aminoglycoside [18]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
plus
Gentamicin 75 mgkg per day IV in 3 divided doses or amikacin 15 to 225 mgkg per
day IV (maximum dose 15 gday) in 3 divided doses
CSF leak mdash Patients with a CSF leak (CSF rhinorrhea or otorrhea) should be treated for
presumed pneumococcal meningitis since S pneumoniae is the most likely organism in this
setting Pneumococcal meningitis in these patients is usually less severe than that caused by
hematogenous invasion and the prognosis is somewhat better Nevertheless because of the
possibility of an isolate highly resistant to penicillin such patients should be treated with a
third-generation cephalosporin plus vancomycin until culture results return This regimen
also will cover H influenzae which rarely causes meningitis in patients with dural defects
(See Empiric regimen above)
Epidemics mdash The empiric treatment of bacterial meningitis during epidemics in which N
meningitidis is suspected is discussed separately (See Treatment and prevention of
meningococcal infection)
SPECIFIC THERAPY mdash Once the causative agent and its in vitro antimicrobial susceptibility
pattern are known empiric antimicrobial therapy can be altered accordingly
S pneumoniae mdash The treatment of pneumococcal meningitis is discussed in detail
separately (See Pneumococcal meningitis in children section on Overview of treatment)
Therapeutic options for pneumococcal meningitis according to antibiotic susceptibility profiles
are outlined in the table (table 1) The usual duration of therapy in uncomplicated cases of S
pneumoniae meningitis is 10 to 14 days
N meningitidis mdash Meningococcal meningitis is best treated with penicillin
Penicillin G 250000 to 300000 Ukg per day IV (maximum 24 million Uday) in 4 or 6
divided doses
A third-generation cephalosporin is an effective alternative to penicillin for children with
penicillin allergy that is not characterized by anaphylaxis [2627] (See Allergy to penicillins
and Penicillin-allergic patients Use of cephalosporins carbapenems and monobactams)
Possible regimens include
Cefotaxime 225 to 300 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided
doses or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
For patients with penicillin allergy characterized by anaphylaxis chloramphenicol is a
recommended alternative [27] Desensitizing the patient to the third-generation cephalosporin
is another option
Chloramphenicol 75 to 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4
divided doses
Although scattered cases of N meningitidis resistant to penicillin have been reported such
strains are rare Relative resistance to penicillin occurs more commonly but does not have an
impact on the response to penicillin or cephalosporin therapy [2829] (See Treatment and
prevention of meningococcal infection section on Penicillin)
A five- to seven-day duration of therapy is adequate for meningococcal meningitis and
eradication of the organism from the cerebrospinal fluid (CSF) [27] However neither penicillin
nor chloramphenicol therapy reliably eradicates nasopharyngeal carriage of N meningitidis
Patients treated with penicillin or chloramphenicol should receive antimicrobial therapy to
eradicate nasopharyngeal carriage before hospital discharge to prevent transmission of the
organism to contacts (See Treatment and prevention of meningococcal infection section on
Antimicrobial chemoprophylaxis)
H influenzae type b mdash Ceftriaxone or cefotaxime is the treatment of choice for ampicillin-
resistant H influenzae type b (Hib) meningitis [2030-32]
Cefotaxime 200 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided doses
or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
Ampicillin is effective for susceptible strains
Ampicillin 300 to 400 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6
divided doses
For patients with penicillin allergy characterized by anaphylaxis desensitizing the patient is
one option Chloramphenicol is another
Chloramphenicol 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4 divided
doses
Cefuroxime should not be used to treat Hib meningitis because it is associated with less
rapid sterilization of the CSF and a greater incidence of hearing loss [3031]
Patients with Hib meningitis should be treated for 7 to 10 days Pharyngeal colonization
persists after curative therapy with agents other than ceftriaxone and cefotaxime Patients
who are not treated with ceftriaxone or cefotaxime should receive rifampin before hospital
discharge to prevent transmission of the organism to contacts For patients who are treated
with chloramphenicol rifampin therapy should be delayed until chloramphenicol is
discontinued since concomitant administration of rifampin may reduce serum concentrations
of chloramphenicol [33] (See Prevention of Haemophilus influenzae infection section on
Antibiotic prophylaxis of close contacts)
L monocytogenes mdash L meningitis traditionally has been treated with ampicillin and
gentamicin because resistance to these drugs is quite rare [34] Although gentamicin has
poor CSF penetration it is used for synergy [35]
Ampicillin 300 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative for penicillin-allergic patients
[36] The dose for TMP-SMX is as follows
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses
Meropenem a carbapenem approved for the treatment of pediatric meningitis has excellent
in vitro activity against L monocytogenes It may prove to be useful for listeria infections but
has not yet been approved for this indication Other antibiotics are less effective against L
monocytogenes
The usual duration of therapy for Listeria meningitis is 14 to 21 days
Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus
agalactiae) meningitis is discussed separately (See Group B streptococcal infection in
neonates and young infants section on Treatment)
S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is
nafcillin or oxacillin [1837]
Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or
Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)
The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin
[183738]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some
experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses
(maximum dose 600 mgday) to vancomycin either orally or by intravenous
administration
Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses or
Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day
maximum dose 1200 mgday
Inflammation of the meninges does not appear to affect penetration of linezolid into
the CSF [39-42] Rapid penetration has been demonstrated in children and
adolescents [42] However CSF concentrations are variable and correlation of CSF
and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some
case reports document successful linezolid treatment of staphylococcal meningitis
[3743]
Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated
with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside
often can be discontinued after the first week once the CSF cultures have been documented
to be sterile Consultation with an expert in pediatric infectious diseases is recommended for
children with meningitis caused by a Gram-negative rod One suggested regimen is as
follows
Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided
doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
The American Academy of Pediatrics (AAP) Committee on Infectious Diseases suggests that
dexamethasone therapy may be beneficial in children with Hib meningitis if given before or at
the same time as the first dose of antimicrobial therapy [20] The AAP Committee on
Infectious Diseases suggests that dexamethasone therapy be considered for infants and
children older than six weeks with pneumococcal meningitis after weighing the potential risks
and benefits [21]
In accordance with the AAP Committee on Infectious Diseases we recommend adjunctive
therapy with dexamethasone for children with Hib meningitis We suggest that decisions
regarding the use of dexamethasone in children with pneumococcal meningitis or in those in
whom bacterial meningitis is suspected but the etiology unknown be individualized
depending upon careful analysis of the potential risks and benefits The author of this topic
review usually does not administer dexamethasone to children with suspected pneumococcal
or meningococcal meningitis In the same patients other experts may choose to use
dexamethasone (See Pneumococcal meningitis in children section on Dexamethasone)
Regimen mdash If the decision is made to use dexamethasone dexamethasone should be given
before or concurrently with the first dose of the antimicrobial agent(s) it is probably of no
benefit if given more than 1 hour later [18] The regimen for dexamethasone is
Dexamethasone 015 mgkg per dose every 6 hours for 2 to 4 days [13] Two days of
dexamethasone appear to be as effective as and less toxic than longer courses [22]
Special circumstances mdash The treatment of bacterial meningitis in children with immune
deficiency recent neurosurgery anatomic defects penetrating head trauma CSF leak and
during epidemics requires consultation with an expert in pediatric infectious diseases
Immune deficiency mdash Vancomycin plus either cefotaxime or ceftriaxone given as described
above are reasonable empiric coverage for most children with an underlying defect in host
defense (See Empiric regimen above)
If a Gram-negative rod is observed on Gram stain of the CSF the addition of an
aminoglycoside (eg gentamicin amikacin) to these two agents is recommended (See Gram-
negative rods below)
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 22 5 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Peak and trough serum concentrations must be monitored when aminoglycosides are used
[23]
Cancer and neutropenia mdash In a retrospective case series of 40 cases of bacterial or fungal
meningitis in 36 neutropenic pediatric cancer patients (two-thirds of whom had recent
neurosurgery a central nervous system [CNS] device or CSF leak) S pneumoniae and
Staphylococcus aureus were the two most common isolates [24] Empiric therapy in such
patients should be based upon the Gram stain results Initial therapy typically includes
vancomycin plus an aminoglycoside plus either cefotaxime or ceftriaxone If there is any
concern about Pseudomonas aeruginosa or an increased risk for infection caused by an
extended-spectrum beta-lactamase (ESBL)-producing organism meropenem may be
warranted as an alternative to cefotaxime or ceftriaxone
T cell defects mdash S pneumoniae and L monocytogenes are the most likely causes of
bacterial meningitis in patients with defective cell-mediated immunity [25] To address these
pathogens the empiric regimen for children with defects in T cell immunity should include
vancomycin plus either cefotaxime or ceftriaxone dosed as recommended above and high-
dose ampicillin (see Empiric regimen above) The dose of ampicillin is as follows
Ampicillin 300 to 400 mgkg IV per day (maximum dose 10 to 12 gday) in 4 or 6
divided doses
Recent neurosurgery mdash In addition to the usual nosocomial pathogens that may complicate
any surgical procedure coagulase-negative staphylococci (such as Staphylococcus
epidermidis) and S aureus are important causes of meningitis in patients who have had
recent neurosurgery Patients who undergo operations that involve a prosthetic device such
as a ventricular shunt or drain are clearly at risk for developing infection (See Infections of
central nervous system shunts and other devices)
Patients who have undergone recent neurosurgery also are at increased risk for meningitis
with enteric Gram-negative rods such as E coli and Klebsiella species as well as P
aeruginosa (See Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in this setting usually consists of a combination of a third-generation
cephalosporin and vancomycin In addition an aminoglycoside (eg gentamicin amikacin)
should be added if Gram-negative bacilli are noted on CSF Gram stain
Alternative regimens include
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
The local antibiogram can help to guide which of the agents directed against Gram-
negative organisms might be most appropriate (eg a high rate of resistance to
ceftazidime suggests meropenem is a better choice)
Recent placement of CSF shunt mdash In infants and children who have had recent placement
of a CSF shunt vancomycin plus either cefotaxime or ceftriaxone are recommended [18]
Anatomic defects mdash Children with anatomic defects (eg dermal sinus (picture 1) urinary
tract anomalies) are at increased risk for meningitis with S aureus or coagulase-negative
staphylococcus and enteric Gram-negative rods such as E coli and Klebsiella (See
Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in children with anatomic defects should include vancomycin plus either
cefotaxime or ceftriaxone dosed as recommended above (See Empiric regimen above)
In addition an aminoglycoside (eg gentamicin amikacin) should be added if Gram-negative
bacilli are noted on CSF Gram stain
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 225 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Penetrating head trauma mdash Patients with penetrating head trauma are at risk for meningitis
with S aureus coagulase-negative staphylococci (such as S epidermidis) and aerobic
Gram-negative bacilli including P aeruginosa [18]
Empiric therapy in this setting usually consists of a combination of vancomycin plus an
extended-spectrum cephalosporin (cefepime or ceftazidime) or meropenem plus an
aminoglycoside [18]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
plus
Gentamicin 75 mgkg per day IV in 3 divided doses or amikacin 15 to 225 mgkg per
day IV (maximum dose 15 gday) in 3 divided doses
CSF leak mdash Patients with a CSF leak (CSF rhinorrhea or otorrhea) should be treated for
presumed pneumococcal meningitis since S pneumoniae is the most likely organism in this
setting Pneumococcal meningitis in these patients is usually less severe than that caused by
hematogenous invasion and the prognosis is somewhat better Nevertheless because of the
possibility of an isolate highly resistant to penicillin such patients should be treated with a
third-generation cephalosporin plus vancomycin until culture results return This regimen
also will cover H influenzae which rarely causes meningitis in patients with dural defects
(See Empiric regimen above)
Epidemics mdash The empiric treatment of bacterial meningitis during epidemics in which N
meningitidis is suspected is discussed separately (See Treatment and prevention of
meningococcal infection)
SPECIFIC THERAPY mdash Once the causative agent and its in vitro antimicrobial susceptibility
pattern are known empiric antimicrobial therapy can be altered accordingly
S pneumoniae mdash The treatment of pneumococcal meningitis is discussed in detail
separately (See Pneumococcal meningitis in children section on Overview of treatment)
Therapeutic options for pneumococcal meningitis according to antibiotic susceptibility profiles
are outlined in the table (table 1) The usual duration of therapy in uncomplicated cases of S
pneumoniae meningitis is 10 to 14 days
N meningitidis mdash Meningococcal meningitis is best treated with penicillin
Penicillin G 250000 to 300000 Ukg per day IV (maximum 24 million Uday) in 4 or 6
divided doses
A third-generation cephalosporin is an effective alternative to penicillin for children with
penicillin allergy that is not characterized by anaphylaxis [2627] (See Allergy to penicillins
and Penicillin-allergic patients Use of cephalosporins carbapenems and monobactams)
Possible regimens include
Cefotaxime 225 to 300 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided
doses or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
For patients with penicillin allergy characterized by anaphylaxis chloramphenicol is a
recommended alternative [27] Desensitizing the patient to the third-generation cephalosporin
is another option
Chloramphenicol 75 to 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4
divided doses
Although scattered cases of N meningitidis resistant to penicillin have been reported such
strains are rare Relative resistance to penicillin occurs more commonly but does not have an
impact on the response to penicillin or cephalosporin therapy [2829] (See Treatment and
prevention of meningococcal infection section on Penicillin)
A five- to seven-day duration of therapy is adequate for meningococcal meningitis and
eradication of the organism from the cerebrospinal fluid (CSF) [27] However neither penicillin
nor chloramphenicol therapy reliably eradicates nasopharyngeal carriage of N meningitidis
Patients treated with penicillin or chloramphenicol should receive antimicrobial therapy to
eradicate nasopharyngeal carriage before hospital discharge to prevent transmission of the
organism to contacts (See Treatment and prevention of meningococcal infection section on
Antimicrobial chemoprophylaxis)
H influenzae type b mdash Ceftriaxone or cefotaxime is the treatment of choice for ampicillin-
resistant H influenzae type b (Hib) meningitis [2030-32]
Cefotaxime 200 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided doses
or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
Ampicillin is effective for susceptible strains
Ampicillin 300 to 400 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6
divided doses
For patients with penicillin allergy characterized by anaphylaxis desensitizing the patient is
one option Chloramphenicol is another
Chloramphenicol 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4 divided
doses
Cefuroxime should not be used to treat Hib meningitis because it is associated with less
rapid sterilization of the CSF and a greater incidence of hearing loss [3031]
Patients with Hib meningitis should be treated for 7 to 10 days Pharyngeal colonization
persists after curative therapy with agents other than ceftriaxone and cefotaxime Patients
who are not treated with ceftriaxone or cefotaxime should receive rifampin before hospital
discharge to prevent transmission of the organism to contacts For patients who are treated
with chloramphenicol rifampin therapy should be delayed until chloramphenicol is
discontinued since concomitant administration of rifampin may reduce serum concentrations
of chloramphenicol [33] (See Prevention of Haemophilus influenzae infection section on
Antibiotic prophylaxis of close contacts)
L monocytogenes mdash L meningitis traditionally has been treated with ampicillin and
gentamicin because resistance to these drugs is quite rare [34] Although gentamicin has
poor CSF penetration it is used for synergy [35]
Ampicillin 300 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative for penicillin-allergic patients
[36] The dose for TMP-SMX is as follows
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses
Meropenem a carbapenem approved for the treatment of pediatric meningitis has excellent
in vitro activity against L monocytogenes It may prove to be useful for listeria infections but
has not yet been approved for this indication Other antibiotics are less effective against L
monocytogenes
The usual duration of therapy for Listeria meningitis is 14 to 21 days
Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus
agalactiae) meningitis is discussed separately (See Group B streptococcal infection in
neonates and young infants section on Treatment)
S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is
nafcillin or oxacillin [1837]
Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or
Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)
The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin
[183738]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some
experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses
(maximum dose 600 mgday) to vancomycin either orally or by intravenous
administration
Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses or
Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day
maximum dose 1200 mgday
Inflammation of the meninges does not appear to affect penetration of linezolid into
the CSF [39-42] Rapid penetration has been demonstrated in children and
adolescents [42] However CSF concentrations are variable and correlation of CSF
and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some
case reports document successful linezolid treatment of staphylococcal meningitis
[3743]
Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated
with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside
often can be discontinued after the first week once the CSF cultures have been documented
to be sterile Consultation with an expert in pediatric infectious diseases is recommended for
children with meningitis caused by a Gram-negative rod One suggested regimen is as
follows
Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided
doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
vancomycin plus an aminoglycoside plus either cefotaxime or ceftriaxone If there is any
concern about Pseudomonas aeruginosa or an increased risk for infection caused by an
extended-spectrum beta-lactamase (ESBL)-producing organism meropenem may be
warranted as an alternative to cefotaxime or ceftriaxone
T cell defects mdash S pneumoniae and L monocytogenes are the most likely causes of
bacterial meningitis in patients with defective cell-mediated immunity [25] To address these
pathogens the empiric regimen for children with defects in T cell immunity should include
vancomycin plus either cefotaxime or ceftriaxone dosed as recommended above and high-
dose ampicillin (see Empiric regimen above) The dose of ampicillin is as follows
Ampicillin 300 to 400 mgkg IV per day (maximum dose 10 to 12 gday) in 4 or 6
divided doses
Recent neurosurgery mdash In addition to the usual nosocomial pathogens that may complicate
any surgical procedure coagulase-negative staphylococci (such as Staphylococcus
epidermidis) and S aureus are important causes of meningitis in patients who have had
recent neurosurgery Patients who undergo operations that involve a prosthetic device such
as a ventricular shunt or drain are clearly at risk for developing infection (See Infections of
central nervous system shunts and other devices)
Patients who have undergone recent neurosurgery also are at increased risk for meningitis
with enteric Gram-negative rods such as E coli and Klebsiella species as well as P
aeruginosa (See Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in this setting usually consists of a combination of a third-generation
cephalosporin and vancomycin In addition an aminoglycoside (eg gentamicin amikacin)
should be added if Gram-negative bacilli are noted on CSF Gram stain
Alternative regimens include
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
The local antibiogram can help to guide which of the agents directed against Gram-
negative organisms might be most appropriate (eg a high rate of resistance to
ceftazidime suggests meropenem is a better choice)
Recent placement of CSF shunt mdash In infants and children who have had recent placement
of a CSF shunt vancomycin plus either cefotaxime or ceftriaxone are recommended [18]
Anatomic defects mdash Children with anatomic defects (eg dermal sinus (picture 1) urinary
tract anomalies) are at increased risk for meningitis with S aureus or coagulase-negative
staphylococcus and enteric Gram-negative rods such as E coli and Klebsiella (See
Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in children with anatomic defects should include vancomycin plus either
cefotaxime or ceftriaxone dosed as recommended above (See Empiric regimen above)
In addition an aminoglycoside (eg gentamicin amikacin) should be added if Gram-negative
bacilli are noted on CSF Gram stain
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 225 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Penetrating head trauma mdash Patients with penetrating head trauma are at risk for meningitis
with S aureus coagulase-negative staphylococci (such as S epidermidis) and aerobic
Gram-negative bacilli including P aeruginosa [18]
Empiric therapy in this setting usually consists of a combination of vancomycin plus an
extended-spectrum cephalosporin (cefepime or ceftazidime) or meropenem plus an
aminoglycoside [18]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
plus
Gentamicin 75 mgkg per day IV in 3 divided doses or amikacin 15 to 225 mgkg per
day IV (maximum dose 15 gday) in 3 divided doses
CSF leak mdash Patients with a CSF leak (CSF rhinorrhea or otorrhea) should be treated for
presumed pneumococcal meningitis since S pneumoniae is the most likely organism in this
setting Pneumococcal meningitis in these patients is usually less severe than that caused by
hematogenous invasion and the prognosis is somewhat better Nevertheless because of the
possibility of an isolate highly resistant to penicillin such patients should be treated with a
third-generation cephalosporin plus vancomycin until culture results return This regimen
also will cover H influenzae which rarely causes meningitis in patients with dural defects
(See Empiric regimen above)
Epidemics mdash The empiric treatment of bacterial meningitis during epidemics in which N
meningitidis is suspected is discussed separately (See Treatment and prevention of
meningococcal infection)
SPECIFIC THERAPY mdash Once the causative agent and its in vitro antimicrobial susceptibility
pattern are known empiric antimicrobial therapy can be altered accordingly
S pneumoniae mdash The treatment of pneumococcal meningitis is discussed in detail
separately (See Pneumococcal meningitis in children section on Overview of treatment)
Therapeutic options for pneumococcal meningitis according to antibiotic susceptibility profiles
are outlined in the table (table 1) The usual duration of therapy in uncomplicated cases of S
pneumoniae meningitis is 10 to 14 days
N meningitidis mdash Meningococcal meningitis is best treated with penicillin
Penicillin G 250000 to 300000 Ukg per day IV (maximum 24 million Uday) in 4 or 6
divided doses
A third-generation cephalosporin is an effective alternative to penicillin for children with
penicillin allergy that is not characterized by anaphylaxis [2627] (See Allergy to penicillins
and Penicillin-allergic patients Use of cephalosporins carbapenems and monobactams)
Possible regimens include
Cefotaxime 225 to 300 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided
doses or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
For patients with penicillin allergy characterized by anaphylaxis chloramphenicol is a
recommended alternative [27] Desensitizing the patient to the third-generation cephalosporin
is another option
Chloramphenicol 75 to 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4
divided doses
Although scattered cases of N meningitidis resistant to penicillin have been reported such
strains are rare Relative resistance to penicillin occurs more commonly but does not have an
impact on the response to penicillin or cephalosporin therapy [2829] (See Treatment and
prevention of meningococcal infection section on Penicillin)
A five- to seven-day duration of therapy is adequate for meningococcal meningitis and
eradication of the organism from the cerebrospinal fluid (CSF) [27] However neither penicillin
nor chloramphenicol therapy reliably eradicates nasopharyngeal carriage of N meningitidis
Patients treated with penicillin or chloramphenicol should receive antimicrobial therapy to
eradicate nasopharyngeal carriage before hospital discharge to prevent transmission of the
organism to contacts (See Treatment and prevention of meningococcal infection section on
Antimicrobial chemoprophylaxis)
H influenzae type b mdash Ceftriaxone or cefotaxime is the treatment of choice for ampicillin-
resistant H influenzae type b (Hib) meningitis [2030-32]
Cefotaxime 200 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided doses
or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
Ampicillin is effective for susceptible strains
Ampicillin 300 to 400 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6
divided doses
For patients with penicillin allergy characterized by anaphylaxis desensitizing the patient is
one option Chloramphenicol is another
Chloramphenicol 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4 divided
doses
Cefuroxime should not be used to treat Hib meningitis because it is associated with less
rapid sterilization of the CSF and a greater incidence of hearing loss [3031]
Patients with Hib meningitis should be treated for 7 to 10 days Pharyngeal colonization
persists after curative therapy with agents other than ceftriaxone and cefotaxime Patients
who are not treated with ceftriaxone or cefotaxime should receive rifampin before hospital
discharge to prevent transmission of the organism to contacts For patients who are treated
with chloramphenicol rifampin therapy should be delayed until chloramphenicol is
discontinued since concomitant administration of rifampin may reduce serum concentrations
of chloramphenicol [33] (See Prevention of Haemophilus influenzae infection section on
Antibiotic prophylaxis of close contacts)
L monocytogenes mdash L meningitis traditionally has been treated with ampicillin and
gentamicin because resistance to these drugs is quite rare [34] Although gentamicin has
poor CSF penetration it is used for synergy [35]
Ampicillin 300 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative for penicillin-allergic patients
[36] The dose for TMP-SMX is as follows
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses
Meropenem a carbapenem approved for the treatment of pediatric meningitis has excellent
in vitro activity against L monocytogenes It may prove to be useful for listeria infections but
has not yet been approved for this indication Other antibiotics are less effective against L
monocytogenes
The usual duration of therapy for Listeria meningitis is 14 to 21 days
Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus
agalactiae) meningitis is discussed separately (See Group B streptococcal infection in
neonates and young infants section on Treatment)
S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is
nafcillin or oxacillin [1837]
Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or
Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)
The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin
[183738]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some
experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses
(maximum dose 600 mgday) to vancomycin either orally or by intravenous
administration
Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses or
Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day
maximum dose 1200 mgday
Inflammation of the meninges does not appear to affect penetration of linezolid into
the CSF [39-42] Rapid penetration has been demonstrated in children and
adolescents [42] However CSF concentrations are variable and correlation of CSF
and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some
case reports document successful linezolid treatment of staphylococcal meningitis
[3743]
Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated
with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside
often can be discontinued after the first week once the CSF cultures have been documented
to be sterile Consultation with an expert in pediatric infectious diseases is recommended for
children with meningitis caused by a Gram-negative rod One suggested regimen is as
follows
Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided
doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
staphylococcus and enteric Gram-negative rods such as E coli and Klebsiella (See
Epidemiology and clinical features of gram-negative bacillary meningitis)
Empiric therapy in children with anatomic defects should include vancomycin plus either
cefotaxime or ceftriaxone dosed as recommended above (See Empiric regimen above)
In addition an aminoglycoside (eg gentamicin amikacin) should be added if Gram-negative
bacilli are noted on CSF Gram stain
Gentamicin 75 mgkg per day IV in 3 divided doses or
Amikacin 15 to 225 mgkg per day IV (maximum dose 15 gday) in 3 divided doses
Penetrating head trauma mdash Patients with penetrating head trauma are at risk for meningitis
with S aureus coagulase-negative staphylococci (such as S epidermidis) and aerobic
Gram-negative bacilli including P aeruginosa [18]
Empiric therapy in this setting usually consists of a combination of vancomycin plus an
extended-spectrum cephalosporin (cefepime or ceftazidime) or meropenem plus an
aminoglycoside [18]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses plus
Cefepime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
or meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
plus
Gentamicin 75 mgkg per day IV in 3 divided doses or amikacin 15 to 225 mgkg per
day IV (maximum dose 15 gday) in 3 divided doses
CSF leak mdash Patients with a CSF leak (CSF rhinorrhea or otorrhea) should be treated for
presumed pneumococcal meningitis since S pneumoniae is the most likely organism in this
setting Pneumococcal meningitis in these patients is usually less severe than that caused by
hematogenous invasion and the prognosis is somewhat better Nevertheless because of the
possibility of an isolate highly resistant to penicillin such patients should be treated with a
third-generation cephalosporin plus vancomycin until culture results return This regimen
also will cover H influenzae which rarely causes meningitis in patients with dural defects
(See Empiric regimen above)
Epidemics mdash The empiric treatment of bacterial meningitis during epidemics in which N
meningitidis is suspected is discussed separately (See Treatment and prevention of
meningococcal infection)
SPECIFIC THERAPY mdash Once the causative agent and its in vitro antimicrobial susceptibility
pattern are known empiric antimicrobial therapy can be altered accordingly
S pneumoniae mdash The treatment of pneumococcal meningitis is discussed in detail
separately (See Pneumococcal meningitis in children section on Overview of treatment)
Therapeutic options for pneumococcal meningitis according to antibiotic susceptibility profiles
are outlined in the table (table 1) The usual duration of therapy in uncomplicated cases of S
pneumoniae meningitis is 10 to 14 days
N meningitidis mdash Meningococcal meningitis is best treated with penicillin
Penicillin G 250000 to 300000 Ukg per day IV (maximum 24 million Uday) in 4 or 6
divided doses
A third-generation cephalosporin is an effective alternative to penicillin for children with
penicillin allergy that is not characterized by anaphylaxis [2627] (See Allergy to penicillins
and Penicillin-allergic patients Use of cephalosporins carbapenems and monobactams)
Possible regimens include
Cefotaxime 225 to 300 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided
doses or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
For patients with penicillin allergy characterized by anaphylaxis chloramphenicol is a
recommended alternative [27] Desensitizing the patient to the third-generation cephalosporin
is another option
Chloramphenicol 75 to 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4
divided doses
Although scattered cases of N meningitidis resistant to penicillin have been reported such
strains are rare Relative resistance to penicillin occurs more commonly but does not have an
impact on the response to penicillin or cephalosporin therapy [2829] (See Treatment and
prevention of meningococcal infection section on Penicillin)
A five- to seven-day duration of therapy is adequate for meningococcal meningitis and
eradication of the organism from the cerebrospinal fluid (CSF) [27] However neither penicillin
nor chloramphenicol therapy reliably eradicates nasopharyngeal carriage of N meningitidis
Patients treated with penicillin or chloramphenicol should receive antimicrobial therapy to
eradicate nasopharyngeal carriage before hospital discharge to prevent transmission of the
organism to contacts (See Treatment and prevention of meningococcal infection section on
Antimicrobial chemoprophylaxis)
H influenzae type b mdash Ceftriaxone or cefotaxime is the treatment of choice for ampicillin-
resistant H influenzae type b (Hib) meningitis [2030-32]
Cefotaxime 200 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided doses
or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
Ampicillin is effective for susceptible strains
Ampicillin 300 to 400 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6
divided doses
For patients with penicillin allergy characterized by anaphylaxis desensitizing the patient is
one option Chloramphenicol is another
Chloramphenicol 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4 divided
doses
Cefuroxime should not be used to treat Hib meningitis because it is associated with less
rapid sterilization of the CSF and a greater incidence of hearing loss [3031]
Patients with Hib meningitis should be treated for 7 to 10 days Pharyngeal colonization
persists after curative therapy with agents other than ceftriaxone and cefotaxime Patients
who are not treated with ceftriaxone or cefotaxime should receive rifampin before hospital
discharge to prevent transmission of the organism to contacts For patients who are treated
with chloramphenicol rifampin therapy should be delayed until chloramphenicol is
discontinued since concomitant administration of rifampin may reduce serum concentrations
of chloramphenicol [33] (See Prevention of Haemophilus influenzae infection section on
Antibiotic prophylaxis of close contacts)
L monocytogenes mdash L meningitis traditionally has been treated with ampicillin and
gentamicin because resistance to these drugs is quite rare [34] Although gentamicin has
poor CSF penetration it is used for synergy [35]
Ampicillin 300 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative for penicillin-allergic patients
[36] The dose for TMP-SMX is as follows
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses
Meropenem a carbapenem approved for the treatment of pediatric meningitis has excellent
in vitro activity against L monocytogenes It may prove to be useful for listeria infections but
has not yet been approved for this indication Other antibiotics are less effective against L
monocytogenes
The usual duration of therapy for Listeria meningitis is 14 to 21 days
Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus
agalactiae) meningitis is discussed separately (See Group B streptococcal infection in
neonates and young infants section on Treatment)
S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is
nafcillin or oxacillin [1837]
Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or
Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)
The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin
[183738]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some
experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses
(maximum dose 600 mgday) to vancomycin either orally or by intravenous
administration
Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses or
Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day
maximum dose 1200 mgday
Inflammation of the meninges does not appear to affect penetration of linezolid into
the CSF [39-42] Rapid penetration has been demonstrated in children and
adolescents [42] However CSF concentrations are variable and correlation of CSF
and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some
case reports document successful linezolid treatment of staphylococcal meningitis
[3743]
Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated
with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside
often can be discontinued after the first week once the CSF cultures have been documented
to be sterile Consultation with an expert in pediatric infectious diseases is recommended for
children with meningitis caused by a Gram-negative rod One suggested regimen is as
follows
Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided
doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
Therapeutic options for pneumococcal meningitis according to antibiotic susceptibility profiles
are outlined in the table (table 1) The usual duration of therapy in uncomplicated cases of S
pneumoniae meningitis is 10 to 14 days
N meningitidis mdash Meningococcal meningitis is best treated with penicillin
Penicillin G 250000 to 300000 Ukg per day IV (maximum 24 million Uday) in 4 or 6
divided doses
A third-generation cephalosporin is an effective alternative to penicillin for children with
penicillin allergy that is not characterized by anaphylaxis [2627] (See Allergy to penicillins
and Penicillin-allergic patients Use of cephalosporins carbapenems and monobactams)
Possible regimens include
Cefotaxime 225 to 300 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided
doses or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
For patients with penicillin allergy characterized by anaphylaxis chloramphenicol is a
recommended alternative [27] Desensitizing the patient to the third-generation cephalosporin
is another option
Chloramphenicol 75 to 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4
divided doses
Although scattered cases of N meningitidis resistant to penicillin have been reported such
strains are rare Relative resistance to penicillin occurs more commonly but does not have an
impact on the response to penicillin or cephalosporin therapy [2829] (See Treatment and
prevention of meningococcal infection section on Penicillin)
A five- to seven-day duration of therapy is adequate for meningococcal meningitis and
eradication of the organism from the cerebrospinal fluid (CSF) [27] However neither penicillin
nor chloramphenicol therapy reliably eradicates nasopharyngeal carriage of N meningitidis
Patients treated with penicillin or chloramphenicol should receive antimicrobial therapy to
eradicate nasopharyngeal carriage before hospital discharge to prevent transmission of the
organism to contacts (See Treatment and prevention of meningococcal infection section on
Antimicrobial chemoprophylaxis)
H influenzae type b mdash Ceftriaxone or cefotaxime is the treatment of choice for ampicillin-
resistant H influenzae type b (Hib) meningitis [2030-32]
Cefotaxime 200 mgkg per day IV (maximum dose 12 gday) in 3 or 4 divided doses
or
Ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
Ampicillin is effective for susceptible strains
Ampicillin 300 to 400 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6
divided doses
For patients with penicillin allergy characterized by anaphylaxis desensitizing the patient is
one option Chloramphenicol is another
Chloramphenicol 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4 divided
doses
Cefuroxime should not be used to treat Hib meningitis because it is associated with less
rapid sterilization of the CSF and a greater incidence of hearing loss [3031]
Patients with Hib meningitis should be treated for 7 to 10 days Pharyngeal colonization
persists after curative therapy with agents other than ceftriaxone and cefotaxime Patients
who are not treated with ceftriaxone or cefotaxime should receive rifampin before hospital
discharge to prevent transmission of the organism to contacts For patients who are treated
with chloramphenicol rifampin therapy should be delayed until chloramphenicol is
discontinued since concomitant administration of rifampin may reduce serum concentrations
of chloramphenicol [33] (See Prevention of Haemophilus influenzae infection section on
Antibiotic prophylaxis of close contacts)
L monocytogenes mdash L meningitis traditionally has been treated with ampicillin and
gentamicin because resistance to these drugs is quite rare [34] Although gentamicin has
poor CSF penetration it is used for synergy [35]
Ampicillin 300 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative for penicillin-allergic patients
[36] The dose for TMP-SMX is as follows
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses
Meropenem a carbapenem approved for the treatment of pediatric meningitis has excellent
in vitro activity against L monocytogenes It may prove to be useful for listeria infections but
has not yet been approved for this indication Other antibiotics are less effective against L
monocytogenes
The usual duration of therapy for Listeria meningitis is 14 to 21 days
Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus
agalactiae) meningitis is discussed separately (See Group B streptococcal infection in
neonates and young infants section on Treatment)
S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is
nafcillin or oxacillin [1837]
Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or
Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)
The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin
[183738]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some
experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses
(maximum dose 600 mgday) to vancomycin either orally or by intravenous
administration
Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses or
Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day
maximum dose 1200 mgday
Inflammation of the meninges does not appear to affect penetration of linezolid into
the CSF [39-42] Rapid penetration has been demonstrated in children and
adolescents [42] However CSF concentrations are variable and correlation of CSF
and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some
case reports document successful linezolid treatment of staphylococcal meningitis
[3743]
Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated
with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside
often can be discontinued after the first week once the CSF cultures have been documented
to be sterile Consultation with an expert in pediatric infectious diseases is recommended for
children with meningitis caused by a Gram-negative rod One suggested regimen is as
follows
Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided
doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
Ampicillin is effective for susceptible strains
Ampicillin 300 to 400 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6
divided doses
For patients with penicillin allergy characterized by anaphylaxis desensitizing the patient is
one option Chloramphenicol is another
Chloramphenicol 100 mgkg per day IV (maximum dose 2 to 4 g per day) in 4 divided
doses
Cefuroxime should not be used to treat Hib meningitis because it is associated with less
rapid sterilization of the CSF and a greater incidence of hearing loss [3031]
Patients with Hib meningitis should be treated for 7 to 10 days Pharyngeal colonization
persists after curative therapy with agents other than ceftriaxone and cefotaxime Patients
who are not treated with ceftriaxone or cefotaxime should receive rifampin before hospital
discharge to prevent transmission of the organism to contacts For patients who are treated
with chloramphenicol rifampin therapy should be delayed until chloramphenicol is
discontinued since concomitant administration of rifampin may reduce serum concentrations
of chloramphenicol [33] (See Prevention of Haemophilus influenzae infection section on
Antibiotic prophylaxis of close contacts)
L monocytogenes mdash L meningitis traditionally has been treated with ampicillin and
gentamicin because resistance to these drugs is quite rare [34] Although gentamicin has
poor CSF penetration it is used for synergy [35]
Ampicillin 300 mgkg per day IV (maximum dose 10 to 12 gday) in 4 to 6 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Trimethoprim-sulfamethoxazole (TMP-SMX) is an alternative for penicillin-allergic patients
[36] The dose for TMP-SMX is as follows
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses
Meropenem a carbapenem approved for the treatment of pediatric meningitis has excellent
in vitro activity against L monocytogenes It may prove to be useful for listeria infections but
has not yet been approved for this indication Other antibiotics are less effective against L
monocytogenes
The usual duration of therapy for Listeria meningitis is 14 to 21 days
Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus
agalactiae) meningitis is discussed separately (See Group B streptococcal infection in
neonates and young infants section on Treatment)
S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is
nafcillin or oxacillin [1837]
Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or
Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)
The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin
[183738]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some
experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses
(maximum dose 600 mgday) to vancomycin either orally or by intravenous
administration
Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses or
Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day
maximum dose 1200 mgday
Inflammation of the meninges does not appear to affect penetration of linezolid into
the CSF [39-42] Rapid penetration has been demonstrated in children and
adolescents [42] However CSF concentrations are variable and correlation of CSF
and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some
case reports document successful linezolid treatment of staphylococcal meningitis
[3743]
Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated
with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside
often can be discontinued after the first week once the CSF cultures have been documented
to be sterile Consultation with an expert in pediatric infectious diseases is recommended for
children with meningitis caused by a Gram-negative rod One suggested regimen is as
follows
Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided
doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
Group B streptococcus mdash The treatment of group B streptococcal (Streptococcus
agalactiae) meningitis is discussed separately (See Group B streptococcal infection in
neonates and young infants section on Treatment)
S aureus mdash The standard therapy for methicillin-susceptible S aureus (MSSA) meningitis is
nafcillin or oxacillin [1837]
Nafcillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g) or
Oxacillin 150 to 200 mgkg per day in 4 doses (maximum daily dose 12 g)
The preferred therapy for methicillin-resistant S aureus (MRSA) meningitis is vancomycin
[183738]
Vancomycin 60 mgkg per day IV (maximum dose 4 gday) in 4 divided doses Some
experts recommend the addition of rifampin 20 mgkg per day divided in 2 doses
(maximum dose 600 mgday) to vancomycin either orally or by intravenous
administration
Alternative agents for MRSA meningitis include TMP-SMX or linezolid [183738]
TMP-SMX 10 to 12 mgkg of the TMP component and 50 to 60 mgkg of the SMX
component per day in 4 divided doses or
Linezolid lt12 years 30 mgkg per day in 3 doses ge12 years 600 mg twice per day
maximum dose 1200 mgday
Inflammation of the meninges does not appear to affect penetration of linezolid into
the CSF [39-42] Rapid penetration has been demonstrated in children and
adolescents [42] However CSF concentrations are variable and correlation of CSF
and plasma levels is inconsistent Furthermore linezolid is not bactericidal but some
case reports document successful linezolid treatment of staphylococcal meningitis
[3743]
Gram-negative rods mdash Meningitis caused by enteric Gram-negative rods is usually treated
with an extended-spectrum cephalosporin and an aminoglycoside [44] The aminoglycoside
often can be discontinued after the first week once the CSF cultures have been documented
to be sterile Consultation with an expert in pediatric infectious diseases is recommended for
children with meningitis caused by a Gram-negative rod One suggested regimen is as
follows
Cefotaxime 200 to 300 mgkg per day IV (maximum dose 12 gday) in 4 divided
doses or ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 2 divided
doses plus
Gentamicin 75 mgkg per day IV in 3 divided doses
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
Organisms such as P aeruginosa often are resistant to many commonly used antibiotics
Ceftazidime has been the most consistently effective cephalosporin in the treatment of P
aeruginosa infections including meningitis [45]
Ceftazidime 150 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
Meropenem is an effective drug in the treatment of meningitis [46] and is approved by the US
Food and Drug Administration (FDA) for the treatment of bacterial meningitis in children and
adolescents It may be used in patients with ceftazidime-resistant strains of various Gram-
negative rods [47] and is the agent of choice in the treatment of meningitis caused by
extended-spectrum beta-lactamase producing Gram-negative enteric organisms [48] It is
dosed as follows
Meropenem 120 mgkg per day IV (maximum dose 6 gday) in 3 divided doses
A repeat CSF sample should be obtained for culture two to three days into therapy to help
assess the efficacy of treatment
In addition we suggest repeating the CSF analysis near the end of therapy particularly in
young infants to determine whether treatment may be discontinued CSF findings suggestive
of the need for continued therapy include
Percentage of neutrophils gt30 percent or
CSF glucose concentration lt20 mgdL
Occasionally intraventricular administration of an antibiotic (generally an aminoglycoside) for
several days is necessary to sterilize the CSF Intraventricular therapy should be undertaken
in consultation with specialists in pediatric infectious diseases and neurosurgery (See
Diagnosis and treatment of gram-negative bacillary meningitis section on Intrathecal and
intraventricular therapy)
DURATION OF THERAPY mdash The duration of antimicrobial therapy depends upon the
causative organism and the clinical course
Positive CSF culture mdash There is limited evidence from high-quality studies to guide the
duration of treatment for bacterial meningitis We suggest the following durations of therapy
for uncomplicated meningitis caused by the following organisms [2027]
S pneumoniae ndash 10 to 14 days
N meningitidis ndash 5 to 7 days
H influenzae type b (Hib) ndash 7 to 10 days
L monocytogenes ndash 14 to 21 days
S aureus ndash at least 2 weeks
Gram-negative bacilli ndash 3 weeks or a minimum of 2 weeks beyond the first sterile
culture whichever is longer [14]
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
A multicenter trial in resource-limited countries found that outcomes were similar among
children treated with 5 versus 10 days of ceftriaxone for meningitis caused by S pneumoniae
N meningitidis or Hib [49] Children (2 months to 12 years) whose repeat cerebrospinal fluid
(CSF) cultures at 48 to 72 hours were negative and who were ldquoclinically stablerdquo after five days
of ceftriaxone were randomly assigned to an additional five days of therapy with ceftriaxone or
placebo The setting methodology and lack of organism-specific outcome information
preclude generalizability to resource-rich settings [4950] We continue to suggest organism-
specific durations of therapy as outlined above
Outpatient therapy mdash In highly selected patients a portion of antibiotic therapy may be
administered in the outpatient setting [1851] Advantages of completion of therapy in the
outpatient setting include decreased risk of nosocomial infection improved quality of life and
decreased cost of therapy [3352-54] Several observational studies have shown that with
careful selection and close monitoring completion of antimicrobial therapy in the outpatient
setting can be safe and effective [52-54]
One group of investigators used the following criteria for outpatient antimicrobial therapy in
children [52]
Completion of at least six days of inpatient therapy serious adverse complications of
meningitis are exceedingly rare after three or four days of therapy particularly in
children who are clinically well and afebrile [141551]
Afebrile for at least 24 to 48 hours before initiation of outpatient therapy
No significant neurologic dysfunction or focal findings
No seizure activity
Clinical stability
Ability to take fluids by mouth
First dose of outpatient antibiotic is administered in the hospital
Outpatient antibiotic therapy is administered in the office or emergency department
setting or by qualified home health nursing
Daily examination is performed by a clinician
Parents are reliable and have transportation and a telephone
Negative CSF culture mdash For children with negative CSF cultures at 48 to 72 hours the
duration of antibiotic therapy is individualized depending upon the remainder of the CSF
evaluation blood culture result and clinical status
For those who have a normal CSF profile and negative blood and CSF culture we
usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours
of incubation
For those who have a CSF pleocytosis and positive blood culture but negative CSF
culture treat for meningitis caused by the organism isolated from the blood culture
(ie management is the same as if the CSF culture was positive for the same
organism)
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
For those who have a CSF pleocytosis negative blood culture and negative CSF
culture we individualize the duration of meningitic doses of antimicrobial therapy
based on clinical parameters Consultation with a specialist in pediatric infectious
diseases is suggested if the clinician is uncertain how to manage such children
RESPONSE TO THERAPY mdash The response to therapy is monitored clinically (eg fever
curve resolution of symptoms and signs) Repeat examination of the spinal fluid and
neuroimaging may be necessary in some patients In children who had a positive blood
culture at initial evaluation blood cultures should be repeated to document sterility of the
blood stream The follow-up blood culture is usually obtained when it is known that the initial
blood culture is positive
In patients with prolonged obtundation irritability seizures focal neurologic abnormalities or
increased head circumference neurologic complications (eg subdural empyema cerebral
vascular thrombosis ventricular dilation brain abscess) should be considered and
neuroimaging may be warranted (See Neurologic complications of bacterial meningitis in
children)
Duration of fever mdash The duration of fever is typically four to six days after the initiation of
adequate therapy [5556] Fever lasts longer than five days in approximately 13 percent of
patients [57] secondary fever (eg recurrence of fever after being afebrile for at least 24
hours) occurs in approximately 16 percent [5557]
Persistence of fever beyond eight days and secondary fever have a number of causes
including [2355]
Inadequate treatment
Development of nosocomial infection (eg infected intravenous catheters urinary tract
infection viral infection) nosocomial infection is more often associated with
secondary fever than with persistent fever [52]
Discontinuation of dexamethasone
Development of a suppurative complication (pericarditis pneumonia arthritis
subdural empyema)
Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever suppurative and nosocomial complications
should be carefully sought and the need for repeat evaluation of the cerebrospinal fluid (CSF)
considered on an individual basis [51] In many cases a specific cause of prolonged fever
cannot be determined In the patient who is improving daily but has unexplained fever despite
careful evaluation it is thought that the individuals host response to infection is responsible
for the prolonged fever
Repeat CSF analysis mdash Re-examination of the CSF is recommended for patients who have
a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy [18] This
is particularly true for children with cephalosporin-resistant pneumococcal meningitis and for
children with pneumococcal meningitis who were treated with dexamethasone (since
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
dexamethasone may interfere with the ability of the clinician to assess clinical response such
as resolution of fever)
Re-examination of the CSF also may be indicated in children with persistent or recurrent
fever as discussed above (See Duration of fever above)
In addition re-examination of the CSF is necessary after two to three days of treatment for
Gram-negative bacillary meningitis to determine appropriate duration of therapy (See Gram-
negative rods above)
Repeat CSF cultures should be sterile Extension of the duration of therapy is indicated if
organisms are seen on Gram stain or isolated from CSF cultures of the repeat CSF
examination Extension of duration of treatment also is indicated if CSF examination at the
conclusion of the standard duration of treatment shows gt30 percent neutrophils CSF glucose
of lt20 mgdL or CSF-to-blood glucose ratio of lt20 percent respectively [51]
Neuroimaging mdash Neuroimaging (with computed tomography [CT] or magnetic resonance
imaging [MRI]) may be indicated during the course of treatment for acute bacterial meningitis
in the following circumstances (see Neurologic complications of bacterial meningitis in
children) [5155]
Focal neurologic signs increasing head circumference or prolonged obtundation
irritability or seizures (gt72 hours after the start of treatment)
Persistently positive CSF cultures despite appropriate antibiotic therapy
Persistent elevation of CSF neutrophils at the completion of standard duration of
therapy (more than 30 to 40 percent)
Recurrent meningitis (to evaluate the possibility of a communication between the
nasal passage or ear and the meninges) sectional (2 mm) coronal cranial CT has
been reported to be a relatively easy noninvasive method of delineating anatomic
abnormalities in children with recurrent meningitis [58]
In addition neuroimaging of infants with Gram-negative meningitis sometime during their
treatment is recommended to detect hydrocephalus or other complications of the meningitis
[59] This is particularly true for infants with Citrobacter or Enterobacter sakazakii (also known
as Cronobacter) meningitis (See Gram-negative rods above)
PROGNOSIS
Mortality mdash Case fatality rates for meningitis in children older than one month in the United
States range from 0 to 15 percent depending upon the infecting organism and when the
survey was performed [161960-63] Among 2780 children in the United States with bacterial
meningitis between 2001 and 2006 mortality was 42 percent [62]
A meta-analysis of prospectively enrolled cohorts of 4920 children from 1955 to 1993 found a
mortality rate of 48 percent in developed countries and 81 percent in developing countries
[61] The mortality rate in developed countries varied by organism ranging from 38 percent
for H influenzae type b (Hib) to 75 percent for N meningitidis to 153 percent for S
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
pneumoniae [61] In the more recent multicenter pneumococcal meningitis surveillance study
(1993 to 1996) mortality for pneumococcal meningitis was 77 percent in the United States
[19] (See Pneumococcal meningitis in children section on Mortality)
Neurologic sequelae mdash Persistent neurologic sequelae are common in children who survive
an episode of bacterial meningitis (See Neurologic complications of bacterial meningitis in
children section on Incidence)
The possible role of dexamethasone therapy in mitigating neurologic complications of
bacterial meningitis is discussed separately (See Dexamethasone and other measures to
prevent neurologic complications of bacterial meningitis in children section on Efficacy)
Prognostic factors mdash Factors related to the outcome of bacterial meningitis in children
include level of consciousness at the time of admission etiologic agent prolonged or
complicated seizures low cerebrospinal fluid (CSF) glucose concentration delayed
sterilization of the CSF and nutritional status as discussed below [192364-69]
Glasgow coma score ndash In post hoc multivariate analysis of data from 654 children
with bacterial meningitis Glasgow coma score (GCS) (table 2) was the only
independent predictor of death or neurologic sequelae [64]
Etiologic agent ndash The risks of mortality and neurologic sequelae are higher in children
with pneumococcal meningitis than with meningococcal or Hib meningitis [1970]
(See Pneumococcal meningitis in children section on Mortality)
The risk of hearing impairment is also related to etiologic agent Hearing loss occurs
in approximately 31 percent of children with pneumococcal meningitis 11 percent of
children with meningococcal meningitis and 6 percent of children with Hib meningitis
[196771]
Seizures ndash In a multicenter pneumococcal meningitis surveillance study the
occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial
therapy was associated with increased risk of neurologic sequelae [19] In a series of
children with Hib meningitis seizures were associated with subtle cognitive and
learning problems [72]
CSF glucose concentration ndash Decreased CSF glucose concentration (lt20 mgdL [11
mmolL]) at the time of admission appears to be associated with hearing loss
[196566]
Delayed sterilization of the CSF ndash Delayed sterilization of the CSF (persistently
positive culture 16 to 18 hours after the initiation of therapy) is associated with
adverse outcomes including moderate to profound sensorineural hearing loss
seizures hemiparesis and abnormal neurologic findings at the time of discharge [73]
Nutritional status ndash Malnutrition is associated with increased morbidity and mortality
[6869] In a multicenter study of 482 Latin American children with bacterial
meningitis the risk of death was increased among those who were underweight
(odds ratio [OR] 198 255 and 585 in mild moderate and severe underweight
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
respectively) [69] The risk of severe neurologic sequelae was also increased in
severely underweight children (OR 5 95 CI 16-16)
FOLLOW-UP
Hearing evaluation mdash Hearing evaluation should be performed at the time of or shortly after
discharge from the hospital [51] Hearing may be assessed by pure tone audiometry evoked
response audiometry may be used in young children or those who cannot cooperate with pure
tone audiometry Hearing evaluation should be repeated if the results of the initial evaluation
suggest more than a minor conductive hearing loss [51] (See Evaluation of hearing
impairment in children)
Development mdash Young children who have been treated for meningitis are at risk for
developmental delay Those who are younger than three years of age may be eligible to
receive Early Intervention Services in the United States (eligibility criteria vary by state)
Appropriate referrals should be made as indicated Developmental surveillance should
continue throughout childhood (See Developmental-behavioral surveillance and screening in
primary care section on When to perform developmental-behavioral screening)
PREVENTION
Isolation mdash All patients admitted to the hospital with meningitis should be placed on standard
precautions [202127] (See General principles of infection control section on Standard
precautions)
In addition droplet precautions are recommended for patients with N meningitidis and H
influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy
[2027] Patients should be in private rooms and hospital personnel should wear a face mask
when they are within 3 feet (1 meter) of the patient
Chemoprophylaxis mdash Chemoprophylaxis which is recommended for certain contacts of
patients with meningococcal and Hib meningitis is discussed separately (See Treatment
and prevention of meningococcal infection section on Antimicrobial chemoprophylaxis and
Prevention of Haemophilus influenzae infection section on Antibiotic prophylaxis of close
contacts)
Although it does not have a role in preventing the spread of pneumococcal meningitis
chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in
children with functional or anatomic asplenia (See Prevention of sepsis in the asplenic
patient section on Antibiotic prophylaxis and Overview of the management of sickle cell
disease section on Infection prevention)
Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid
(CSF) leaks and predispose patients to meningitis because of the potential for direct
communication of bacteria in the upper respiratory tract with the central nervous system
There is no evidence that antibiotics given prophylactically are efficacious for preventing
meningitis [74]
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
Vaccines mdash Vaccines directed against each of the major pathogens causing bacterial
meningitis in children are discussed separately
S pneumoniae (see Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children and Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children section on Indications)
N meningitidis (see Meningococcal vaccines and Patient information Vaccines for
children age 7 to 18 years (Beyond the Basics))
Hib (see Prevention of Haemophilus influenzae infection section on Immunization
and Patient information Vaccines for infants and children age 0 to 6 years (Beyond
the Basics))
INFORMATION FOR PATIENTS mdash UpToDate offers two types of patient education
materials ldquoThe Basicsrdquo and ldquoBeyond the Basicsrdquo The Basics patient education pieces are
written in plain language at the 5th to 6th grade reading level and they answer the four or five
key questions a patient might have about a given condition These articles are best for
patients who want a general overview and who prefer short easy-to-read materials Beyond
the Basics patient education pieces are longer more sophisticated and more detailed These
articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon
Here are the patient education articles that are relevant to this topic We encourage you to
print or e-mail these topics to your patients (You can also locate patient education articles on
a variety of subjects by searching on ldquopatient infordquo and the keyword(s) of interest)
Basics topics (see Patient information Meningitis in children (The Basics) and
Patient information Bacterial meningitis (The Basics))
Beyond the Basics topic (see Patient information Meningitis in children (Beyond the
Basics))
SUMMARY AND RECOMMENDATIONS
Immediate and supportive care
Antibiotic therapy should be initiated immediately after the lumbar puncture (LP) is
performed if the clinical suspicion for meningitis is high (algorithm 1) (See Avoidance
of delay above)
The pretreatment evaluation of children with suspected bacterial meningitis should
include a complete history and physical examination cerebrospinal fluid (CSF)
examination (cell count and differential glucose protein Gram stain and culture)
complete blood count (CBC) with differential and platelet count blood cultures serum
electrolytes glucose blood urea nitrogen creatinine evaluation of clotting function is
indicated if petechiae or purpuric lesions are noted (algorithm 1) (See Pretreatment
evaluation above)
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
Immediate management of children with suspected bacterial meningitis includes
assessment and stabilization of ventilation and perfusion and initiation of
hemodynamic monitoring and support while obtaining appropriate laboratory studies
and establishing venous access Empiric antibiotic therapy and dexamethasone if
warranted should be administered as soon as possible after lumbar puncture
Hypoglycemia acidosis and coagulopathy should be treated as necessary (See
Immediate management above)
For children who are neither in shock nor dehydrated we suggest moderate fluid
restriction (1200 mLm2 per day) until evidence of inappropriate secretion of
antidiuretic hormone can be excluded (Grade 2B) (See Fluid management above)
Antibiotic and dexamethasone therapy
We recommend that the empiric regimen for infants and children older than one
month with bacterial meningitis include coverage for antibiotic-resistant Streptococcus
pneumoniae Neisseria meningitidis and Haemophilus influenzae type b (Hib) (Grade
1A) (See Major pathogens above and Empiric regimen above)
An appropriate empiric regimen includes vancomycin 60 mgkg per day IV (maximum
dose 4 gday) in 4 divided doses plus high doses of either cefotaxime 300 mgkg per
day intravenously (IV) (maximum dose 12 gday) in 3 or 4 divided doses or
ceftriaxone 100 mgkg per day IV (maximum dose 4 gday) in 1 or 2 divided doses
(See Empiric regimen above)
We recommend the use of dexamethasone for children with Hib meningitis (Grade
1A) (See Use of dexamethasone above and Dexamethasone and other measures
to prevent neurologic complications of bacterial meningitis in children section on
Dexamethasone)
Decisions regarding the use of dexamethasone in children with pneumococcal
meningitis or in whom bacterial meningitis is suspected but the etiology unknown
must be individualized after careful analysis of the potential risks and benefits The
author of this topic review usually does not administer dexamethasone to children
with suspected pneumococcal or meningococcal meningitis In the same patients
other experts may choose to use dexamethasone (See Use of dexamethasone
above and Pneumococcal meningitis in children section on Dexamethasone and
Dexamethasone and other measures to prevent neurologic complications of
bacterial meningitis in children section on Dexamethasone)
We recommend not using dexamethasone if more than one hour has elapsed since
the first dose of antimicrobial therapy (Grade 1A) (See Use of dexamethasone
above and Dexamethasone and other measures to prevent neurologic complications
of bacterial meningitis in children section on Dexamethasone)
The empiric regimen may need to be broadened in infants and children with immune
deficiency recent neurosurgery penetrating head trauma and anatomic defects
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19
Patients with these conditions should be managed in consultation with a specialist in
pediatric infectious diseases (See Special circumstances above)
Once the causative agent and its in vitro antimicrobial susceptibility pattern are
known empiric antimicrobial therapy can be altered accordingly (See Specific
therapy above)
The duration of antimicrobial therapy depends upon the causative organism and the
clinical course (See Duration of therapy above)
Response to treatment
The response to therapy is monitored clinically (eg fever curve resolution of
symptoms and signs) Repeat examination of the spinal fluid may be necessary in
some patients (See Response to therapy above)
Re-examination of CSF is indicated for patients who have a poor clinical response
despite 24 to 36 hours of appropriate antimicrobial therapy This is particularly true for
children with third-generation cephalosporin-resistant pneumococcal meningitis and
for children with pneumococcal meningitis who were treated with dexamethasone In
addition re-examination of the CSF is necessary after two to three days of treatment
for Gram-negative bacillary meningitis to determine appropriate duration of therapy
(See Repeat CSF analysis above and Gram-negative rods above)
Neuroimaging is indicated in infants and children with signs or symptoms of
complications andor recurrent meningitis (See Neuroimaging above)
Prognosis and follow-up
The overall mortality for bacterial meningitis in infants and children is approximately 5
percent in developed countries and 8 percent in developing countries (See Mortality
above)
Neurologic sequelae including deafness intellectual disability spasticity andor
paresis and seizures occur in 15 to 25 percent of survivors (See Neurologic
sequelae above)
Children who have been treated for bacterial meningitis should undergo hearing
evaluation at the time of or shortly after discharge They should also be followed
closely for other neurologic sequelae including gross motor and cognitive impairment
(See Follow-up above)
Antibiotic prophylaxis
Chemoprophylaxis is recommended for certain contacts of patients with
meningococcal meningitis and Hib meningitis (See Prevention of Haemophilus
influenzae infection section on Antibiotic prophylaxis of close contacts and
Treatment and prevention of meningococcal infection section on Antimicrobial
chemoprophylaxis)
Use of UpToDate is subject to the Subscription and License Agreement Topic 6010 Version 19