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Non-tuberculous bacterial meningitis

INTRODUCTION'Meningitis' refers to inflammation of the pia andarachnoid membranes of the brain and spinal cord and thefluid in the spaces they enclose. This is usually caused bybacteria and occasionally by viruses and fungi. In westerncountries there are 4 to 5 cases of meningitis per 100 000population annually and their patients have a mortality of6%. The incidence of bacterial meningitis in India andother developing countries is probably similar, but themortality is higher.

Neisseria meningitidis is often responsible for epidemicsof meningitis and this organism together with Haemophilusinfluenzae and Streptococcus pneumoniae is responsible for60% to 80% of community-acquired bacterial meningitis.Pathogens which cause disease more commonly in certainage groups are listed in Table I. Meningitis occurs parti-cularly easily if the host is immunocompromised or if the

TABLE I. Organisms which commonly cause meningitis accordingto age

Neonates Gram-negative organismsespecially E. coli. Klebsiella and H. influenzae

H. influenzae, meningococcus

Meningococcus, pneumococcus

Pre-school children

School children andyoung adults

Elderly

All ages

Pneumococcus

Streptococcus, Staphylococcus,Gram-negative bacilli

Immunocompromised Any organism induding Listeria monocytogenes

meningeal coverings have been disrupted. In theseinstances disease may be produced by bacteria which arenot pathogenic under ordinary circumstances. Severalconditions predispose to bacterial meningitis (Table II).

TABLE II. Predisposing causes of bacterial meningitis

MalignancyCollagen diseaseLeukaemia and Iymphoreticular diseaseRenal dialysisOrgan transplantsSteroid therapyImmunosuppression/cytotoxic drugsAlcoholism

Diabetes mellitusBase of skull fractures

Fractures of the base of the skuIl which result in cerebro-spinal fluid (CSF) rhinorrhoea are a common cause ofrecurrent meningitis.

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CLINICAL FEATURESFever, headache and vomiting are the usual symptoms ofmeningitis. Less commonly, the patient may present withconfusion and varying degrees of altered sensorium. Theonset of illness can be either acute or gradual. When theonset is gradual it may be 4 or 5 days before the patientseeks medical help. Signs of meningeal irritation, such asneck rigidity and Kernig's sign, which are the hallmarksof meningitis, can be absent in the very young, particularlyin neonates, in the very old and in immunocompromisedindividuals. It is important to remember that septicaemia,failure to thrive, temperature imbalance or jaundice maybe the presenting symptoms of meningitis in neonates.The fontanelles are usually tense. CSF examination isnecessary to establish the diagnosis. Meningococcalmeningitis is often associated with purpuric skin rashes(Fig. 1) and occasionally with disseminated intravascularcoagulation, circulatory collapse, arthritis and cutaneousherpes simplex lesions while pneumococcal meningitisshould be suspected if there has been preceding infectionin the lungs, ears, sinuses or heart valves, in patients whohave had a previous splenectomy, in patients with basal

FIG 1. Purpuric skin rash of meningococcal meningitis

skull fractures and in alcoholics. In children H. influenzaemeningitis usually follows infections of the upper respira-tory tract and ear.

Sometimes a cerebral abscess develops when arterialinflammation produces a focus of ischaemic or necroticbrain tissue which acts as a nidus in which organisms canproliferate. Cerebral abscesses are often associated withmiddle ear and paranasal sinus infections, septicaemiaand skull fractures. The arterial involvement may producehemiparesis or monoparesis. Focal seizures are often aresult of superficial cortical thrombophlebitis secondaryto leptomeningeal inflammation. Infection of the duralsinus is rare. Hydrocephalus is the result of obstruction tothe CSF pathway. Subdural empyema is usually associatedwith paranasal and ear infections; it should be suspectedif meningitis is associated with a markedly raised intra-cranial pressure, seizures or focal neurological deficits. Acr scan of the head is the investigation of choice fordetecting subdural empyema (Fig. 2).

EVERYDA Y PRACTICE

FIG 2. CT scan showing subduralempyema

The level of consciousness is an important determinantof prognosis. With decreasing levels of consciousness,mortality rises and may be as high as 50% to 60% indeeply comatose patients. Generalized seizures arecommon in neonates and infants while in adults focalseizures are more common. Generalized seizures in adultsmay be associated with hemiparesis (Todd's phenomenon).Cranial nerve involvement, especially of the ocular nerves,is not unusual and is due to vasculitis, basal exudationor brainstem distortion caused by a raised intracranialpressure. Papilloedema, the result of either a raisedintracranial pressure or severe bilateral optic neuritis, isseen in about 15% to 20% of patients with meningitis.

DIAGNOSISA high index of clinical suspicion is the primary requisitefor the diagnosis of meningitis. The diagnosis can be con-firmed by the characteristic findings in the CSF obtainedby a lumbar puncture (LP). It is a simple procedure andone should not hesitate to do it. (The technique and itscomplications are described in detail on pages 37-9.)The risk of transtentorial herniation is real in patients withpapilloedema or focal neurological signs. In such situations,the physician is faced with a dilemma: the urgent need toconfirm the diagnosis and identify the causative organismso that appropriate treatment can be started as against thehazards of an LP in the presence of a raised intracranialpressure.

In bacterial meningitis, the CSF shows leucocytosis(1000 to 100 ()()() cells per ml) with a predominance ofpolymorphonuclear leucocytes (85% to 95%). Theprotein is elevated (1O~500 mg%) and the glucosereduced «40% of a simultaneously obtained bloodsugar value). A gram stain of the CSF is a rapid means ofidentifying the causative organism (Fig. 3). Positive identifi-cation rates vary from less than 40% to as high as 80%.The test is simple and results are available immediately.CSF culture takes 24 to 48 hours and is therefore of littlehelp in urgent management. Cultures for anaerobicorganisms should always be done.

Patients with meningitis who come for evaluation after

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FIG 3. Gram stain of CSF showing gram-positive diplococci

receiving subtherapeutic and incomplete courses of anti-microbial therapy pose diagnostic problems. The CSF insuch cases shows a lymphocytic predominance and makesthe distinction from tuberculous meningitis difficult.The bromide partition test, which relies on the increasedpermeability of the blood-brain barrier to bromide, helpsdifferentiate tuberculous meningitis from viral and, to alesser extent, from other bacterial causes of meningitis. Insuch situations immunological tests may be helpful forestablishing the cause. Counterimmunoelectrophoresis isespecially useful in pneumococcal, meningococcal andhaemophilus infections. Latex agglutination is anotherrapid and useful test. Non-immunological tests such as theIimulus lysate test have a high positive predictive valuein bacterial meningitis. Indirect evidence of anaerobicbacterial infections can be obtained by estimating CSFlactic acid, butyrate and acetate levels. In practice all thetests mentioned may give equivocal results and one maybe forced into initiating treatment with drugs for bothpyogenic and tuberculous meningitis. Evidence of tuber-culosis elsewhere in the patients and a strongly positiveMantoux test point to a tuberculous aetiology.

ROLE OF CT SCANThe advent of the CT scan has made it possible to detectmany of the neurological complications of meningitissafely. These are listed in Table II I.

TABLE III. Complications of bacterial meningitis

Neurological

Cerebral abscess

Subdural effusion or empyema

Cerebral infarction

Non-neurological

Shock

Adrenal failure

Disseminated intravascularcoagulation

Dural sinus thrombosis

Hydrocephalus

Cranial nerve palsies

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TREATMENTMeningitis acquired in the community in the non-immunocompromised host is most often caused byH. influenzae, meningococci or streptococci. It should beremembered that meningococci are becoming increasinglyresistant to sulphonamides and H. influenzae to ampicillin.Benzylpenicillin can be used to initiate treatment inmeningococcal and pneumococcal infections and whengram-negative organisms are responsible for meningitis inschool going or older subjects. Chloramphenicol shouldbe used in H. influenzae infections or when gram-negativeorganisms are causative in children below five.

Many physicians prefer to combine chloramphenicol(100 mglkglday) with either penicillin (150 mglkglday) orampicillin (200 mglkglday) as the first line of treatment.These drugs are preferably given intravenously, althoughthe intramuscular route can also be used. Chloramphenicolcrosses the blood-brain barrier readily. Rarely, intrathecaladministration of antibiotics is justified if deteriorationcontinues despite use of appropriate antimicrobials givenin adequate doses. Meningitis complicating a neurosurgicalprocedure is usually caused by gram-negative bacilli orStaphylococcus aureus. Treatment with an amino-glycoside (gentamycin, tobramycin) preferably givenintrathecally, combined with a penicillinase-resistantpenicillin (nafcillin), is appropriate. Cephalosporins suchas cefotaxime and ceftazimide are very effective againstgram-negative bacilli and should be used when the diseaseis caused by chloramphenicol-resistant organisms. Otherpromising drugs include the quinolones. Table IV lists thedoses of some drugs used in meningitis.

Therapy should be continued for at least 10 to 14days.By this time the patient has usually been afebrile for 3 to 4days and is totally asymptomatic. A repeat lumbar punctureis not essential to determine whether therapy can be stop-ped as quite often the CSF does show raised cells andproteins for several weeks after clinical recovery.

Recurrent meningitis is often seen with compound skullfractures or congenital malformations such as dermal

Surgical management of bacterialmeningitis

Although antimicrobial therapy is the mainstay of manage-ment of bacterial meningitis, surgical intervention issometimes necessary for the indications given in Table I.

COMPLICATIONS OF MENINGITIS

HydrocephalusThis is probably the commonest indication for operationin a patient with bacterial meningitis. Ventricular enlarge-

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TABLE IV. Antibiotic dosages for bacterial meningitis

Antibiotic Adults ChildrenTotal Interval Total Interval(per day) (hours) (per day) (hours)

Ampicillin 12g 4 200-300mg/kg 6Carbenicillin 3O-4Og 4--{) 400-500 mg/kg 4Nafcillin 12-ISg 4 150-200 mg/kg 4--{)

PenicillinG 20-24 x 10" 2-4 20-30 x io- 4--{)

units unitsCefotaxime 12g 4 150-200 mg/kg 4--{)

Ceftazimide 6g 8 lOO-I50mglkg 8Cefuroxirne 4.5-9g 8 200-240 mglkg 6Chloramphenicol 4g 6 lOOmglkg 6Amikacin

Intravenous 15mglkg S-12 15mgikg S-12Intraventricular 20-30 mg 24 4-5mg 24

GentamicinIntravenous 5mglkg 8 5-7mglkg SIntraventricular S-IO mg 24 2-2.5mg 24

sinuses or neuroenteric cysts. These patients require earlysurgical repair of the communication between theneuroaxis and the exterior soon after the meningitis hasbeen eradicated with appropriate antimicrobial drugs.

An occasional patient with bacterial meningitisdevelops marked brain swelling. In such instances,intravenous mannitol (0.25 to 5.0 glkg) given over half anhour may be life saving. If seizures develop, these shouldbe treated with diazepam (5 to 10 mg intravenously) orwith phenytoin. Sedation should be avoided because ofthe risk of aspiration pneumonia.

P. P.ASHOKP.D. Hinduja National Hospital

Bombay 400016India

TABLE I. Indications for surgery in bacterial meningitis

Complications of meningitisI. Hydrocephalus2. Subdural effusion/empyema3. Rarer complications

a. Brain abscessb. Optochiasmatic

arachnoiditis

Closure of fistulaeI. CSF rhinorrhoea/otorrhoea2. Dermal sinuses

a. Lumbosacralb. Occipital

Eradication of focus of infectionI. Otitis media2. Paranasal sinusitis3. Miscellaneous

a. Cranial osteomyelitisb. Pulmonaryc. Cardiac

MiscellaneousI. Removal of foreign bodies

a. Shunt tubesb. Cranioplasty platesc. Dural substitutes