Suspected Staphylococcus aureus skin and soft tissue infections_ Evaluation and management in...

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6/20/2016 Suspected Staphylococcus aureus skin and soft tissue infections: Evaluation and management in neonates

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Official reprint from UpToDatewww.uptodate.com 2016 UpToDate

AuthorSheldon L Kaplan, MD

Section EditorMorven S Edwards, MD

Deputy EditorMary M Torchia, MD

Suspected Staphylococcus aureus skin and soft tissue infections: Evaluation and management in neonates

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: May 2016. | This topic last updated:Apr 15, 2016.

INTRODUCTION The evaluation and management of suspected methicillin-resistant Staphylococcus aureus (MRSA)

skin and soft tissue infections (SSTI) in neonates (28 days of age) will be reviewed here. General aspects of the

management of SSTI the evaluation and management of MRSA SSTI in children older than 28 days the epidemiology,

prevention, and control of MRSA infections in children and the treatment of invasive MRSA infections in children and are

discussed separately.

EVALUATION

History and examination The history and examination of the neonate with suspected S. aureus SSTI focus on

consideration of other causes of SSTI in neonates, particularly those with vesicopustular lesions that may require other

types of antimicrobial therapythan S. aureus infections (table 1). (See "Vesiculobullous and pustular lesions in the

newborn".)

Important aspects of the clinical evaluation include:

Laboratory evaluation

(See "Cellulitis and erysipelas".)

(See "Impetigo".)

(See "Infectious folliculitis".)

(See "Skin abscesses, furuncles, and carbuncles".)

(See "Suspected methicillin-resistant Staphylococcus aureus skin and soft tissue infections: Evaluation and

management in children >28 days".)

(See "Methicillin-resistant Staphylococcus aureus infections in children: Epidemiology and clinical spectrum".)

(See "Methicillin-resistant Staphylococcus aureus in children: Prevention and control".)

(See "Methicillin-resistant Staphylococcus aureus in children: Treatment ofinvasive infections".)

Systemic symptoms and signs (eg, ill-appearance, fever/hypothermia, irritability, poor feeding.

Risk factors for sepsis and herpes simplex virus (HSV), which are discussed separately. (See "Clinical features,

evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Maternal risk factors' and "Clinical

features and diagnosis of bacterial sepsis in the preterm infant (


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MANAGEMENT APPROACH The safety and efficacy of topical, oral, and parenteral therapy for community-

associated methicillin-resistant S. aureus infections have not been well evaluated in neonates. The approach described

below is consistent with that provided by the Infectious Diseases Society of America (IDSA) [ 1], which is based uponobservations from a review of 126 cases treated between 2001 and 2006 at the author's institution [ 3]. Additional

considerations include the increased risk of sepsis in neonates (given the immaturity of their immune system) and the

inability to accurately predict serious bacterial infection according to clinical features or clinical decision rules. (See

"Strategies for the evaluation of febrile young infants (7 to 90 days of age)", section on 'Limitations in neonates' .)

Localized pustulosis

SSTI other than localized pustulosis We hospitalize preterm/very low-birth weight neonates and term neonates with

SSTI other than localized pustulosis (eg, multiple sites of pustulosis, mastitis and other sites of cellulitis, abscess) for

close monitoring and parenteral antimicrobial therapy [3]. Infants 28 days are at increased risk for invasive infection.

Such neonates typically have undergone evaluation for one or more concomitant serious bacterial infection (eg,

bacteremia, urinary tract infection, meningitis, osteoarticular infection) and are treated with parenteral antimicrobial therapy

until 48-hour culture results are available.

In addition to provision of parenteral antimicrobial therapy, we recommend drainage of purulent or fluctuant lesions (eg,

cutaneous abscess).

Other studies Our approach to obtaining other laboratory studies and cultures in neonates with suspected S.

aureus SSTI depends upon the type of infection and associated clinical features:

Neonates with mastitis The evaluation of neonates with mastitis is discussed separately. (See "Mastitis and

breast abscess in infants, children, and adolescents", section on 'Infants


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ANTIMICROBIAL THERAPY

Initial parenteral therapy Empiric parenteral antibiotics for suspected staphylococcal SSTI in neonates should be

based upon the local susceptibility pattern of community-associated S. aureus isolates. When the etiologic agent and

susceptibility are known, antimicrobial therapy can be narrowed as indicated.

For neonates with suspected staphylococcal infection limited to the skin and soft tissues, we provide initial empiric

coverage for methicillin-resistant S. aureus (MRSA) with vancomycin, clindamycin, or linezolid [1,3]. In communities

where MRSA is less prevalent, initial empiric coverage for methicillin-susceptible S. aureus(eg, nafcillin, oxacillin) is an

alternative (table 3).

For infants with suspected staphylococcal infection who are febrile, have other systemic findings, or are admitted to the

hospital, it is usually necessary to add coverage for other neonatal pathogens (eg, gentamicin or cefotaximefor enteric

gram negative pathogens). The combination of vancomycin plus either cefotaxime or gentamicin provides adequate

empiric therapy for possible group B streptococcal cellulitis, but is not appropriate for sepsis or meningitis. (See "Clinical

features, evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Etiologic agents' and

"Management and outcome of sepsis in term and late preterm infants", section on 'Initial empiric therapy' and "Group B

streptococcal infection in neonates and young infants", section on 'Antimicrobial therapy' .)

Duration of therapy

RESPONSE TO THERAPY

Monitoring response Response to therapy is indicted by clinical improvement after 48 hours. In neonates who are

admitted to the hospital for antimicrobial therapy, we monitor the SSTI for improvement or progression, the patient's vital

signs, and culture and susceptibility results (if obtained).

Neonates who are treated for methicillin-resistant S. aureus (MRSA) in the outpatient setting should be instructed to seek

medical care promptly if they develop systemic symptoms or if local symptoms worsen [8]. They should be seen for

follow-up within 48 hours. Follow-up is essential to ensure clinical improvement and determine the need for additional

drainage or change in antimicrobial therapy.

Failure to respond Initiation of systemic therapy (for neonates initially treated with topical antibiotics) or change in

antimicrobial therapy (guided by culture and susceptibility results, if available) may be warranted for patients who have not

Isolated SSTI The total duration of therapy for staphylococcal SSTI in neonates depends upon clinical response a

total of 7 to 14 days is usually adequate if there are no complications [3].

We continue parenteral therapy for infants with isolated SSTI at least until all of the following criteria are met:

Resolution of systemic symptoms and fever

Improvement in other clinical findings

Antibiotic susceptibility results are available

Systemic bacterial cultures (urine, blood, cerebrospinal fluid) isolate no pathogens during at least 48 hours of

incubation

Results of antibiotic susceptibility testing should be used to make decisions about which oral antibiotic to use for

continuation of systemic therapy.

Appropriate oral agents for neonates with SSTI include cephalexin and clindamycin, depending upon the

susceptibilities of the S. aureus that is isolated (table 3) [ 6,7]. Linezolid may be used when the isolate is resistant to

other agents, but should be used under close supervision by an expert in infectious diseases [3].

Trimethoprim-sulfamethoxazole should not be used in neonates because it may displace bilirubin, increasing the risk

for bilirubin toxicity. (See "Evaluation of unconjugated hyperbilirubinemia in term and late preterm infants", section on

'Bilirubin/albumin ratio'.)

Invasive infection Antimicrobial therapy for neonates with invasive staphylococcal infections that have extended

beyond the skin and soft tissues is discussed separately. (See "Methicillin-resistant Staphylococcus aureus in

children: Treatment of invasive infections", section on 'Treatment of neonates'.)
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improved after 48 hours of observation or antimicrobial therapy.

Possible explanations for failure to respond in neonates receiving an agent to which their isolate is susceptible include

inadequate drainage (if drainage was performed), abscess recurrence, or development of a new abscess. Ultrasonography

may identify residual, recurrent, or new abscesses that require drainage.

If cultures remain negative and ultrasonography does not identify lesions that require drainage, a change in empiric therapy

may be indicated (eg, to include coverage for MRSA if MRSA was not initially included). In such cases, consultation with

an expert in infectious diseases is suggested.

INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyondthe Basics." The Basics patient education pieces are written in plain language, at the 5 to 6 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 10 to 12 grade reading level

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REFERENCES

th th

th th

Basics topics (see "Patient information: Methicillin-resistant Staphylococcus aureus (MRSA) (The Basics)")

Beyond the Basics topic (see "Patient information: Methicillin-resistant Staphylococcus aureus (MRSA) (Beyond the

Basics)")

The history and examination of the neonate with suspected Staphylococcus aureusskin and soft tissue infection

(SSTI) focus on consideration of other causes of SSTI in neonates, particularly those with vesicopustular lesions

that require other types of antimicrobial therapy than S. aureus infections (table 1). (See 'History and examination'

above.)

We obtain specimens for Gram stain, culture, and susceptibility testing from neonates with purulent/fluctuant skin

lesions (abscess) if purulent material can be obtained. Our approach to obtaining other laboratory studies and

cultures in neonates with suspected S. aureus SSTI depends upon the type of infection and associated clinicalfeatures. (See 'Laboratory evaluation' above.)

We suggest that localized pustulosis (picture 1) in full-term neonates without fever or other signs or symptoms of

infection be treated with topical antibiotic therapy in the outpatient setting ( Grade 2C). We typically use mupirocin

three times daily for 5 to 10 days. Close outpatient follow-up is essential. (See 'Localized pustulosis' above.)

We recommend hospital admission and parenteral antimicrobial therapy for local pustulosis in preterm or very low-

birth-weight neonates (Grade 1B). (See 'Localized pustulosis' above.)

We recommend hospital admission for infants 28 days with SSTI more severe than localized pustulosis (eg,

pustulosis in multiple sites, cellulitis, abscess, mastitis) and for those who undergo evaluation for serious bacterial

infection (eg, bacteremia, urinary tract infection, meningitis, arthritis, osteomyelitis) (Grade 1B). (See 'SSTI other

than localized pustulosis' above.)

Empiric parenteral antibiotics for SSTI in neonates should be based upon the local susceptibility pattern of

community-associated S. aureus isolates. In areas with an increased prevalence of methicillin-resistant S. aureus,

vancomycin, clindamycin, and linezolid are appropriate alternatives for infection limited to the skin and soft tissues

gentamicin may be added to broaden coverage (table 3). (See 'Initial parenteral therapy' above.)
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1. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america for thetreatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 201152:e18.

2. American Academy of Pediatrics. Staphylococcal infections. In: Red Book: 2015 Report of the Committee onInfectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy ofPediatrics, 2015. p.715.

3. Fortunov RM, Hulten KG, Hammerman WA, et al. Evaluation and treatment of community-acquired Staphylococcusaureus infections in term and late-preterm previously healthy neonates. Pediatrics 2007 120:937.

4. Miller LG, Perdreau-Remington F, Bayer AS, et al. Clinical and epidemiologic characteristics cannot distinguish

community-associated methicillin-resistant Staphylococcus aureus infection from methicillin-susceptible S. aureusinfection: a prospective investigation. Clin Infect Dis 2007 44:471.

5. Day CT, Kaplan SL, Mason EO, Hulten KG. Community-associated Staphylococcus aureus infections in otherwisehealthy infants less than 60 days old. Pediatr Infect Dis J 2014 33:98.

6.Autret E, Laugier J, Marimbu J, et al. [Comparison of plasma levels of amoxicillin administered by oral andintravenous routes in neonatal bacterial colonization]. Arch Fr Pediatr 1988 45:679.

7. Boothman R, Kerr MM, Marshall MJ, Burland WL. Absorption and excretion of cephalexin by the newborn infant.Arch Dis Child 1973 48:147.

8. Gorwitz RJ. A review of community-associated methicillin-resistant Staphylococcus aureus skin and soft tissueinfections. Pediatr Infect Dis J 2008 27:1.

Topic 106447 Version 3.0
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GRAPHICS

Vesiculopustular lesions in neonates and infants that require treatment

and/or monitoring

Condition Clinical features Significance

Infectious conditions

Congenital

herpes

simplex virus

(HSV)

Grouped or single vesicles on

erythematous base in crops on skin and

mucous membranes lesions usually

appear between one and two weeks of

age may be associated with nonspecific

signs of serious illness: temperature

instability, respiratory distress, poor

feeding, lethargy

Requires antiviral therapy significant

morbidity and mortality if untreated

Neonatal

varicellazoster virus

Grouped or single vesicles on

erythematous base in crops on skin andmucous membranes

Requires antiviral therapy associated with

significant morbidity and mortality

Congenital

syphilis

Blisters, erosions that frequently involve

the palms and soles other manifestations

include rhinitis, anemia, jaundice,

hepatomegaly

Requires antibiotic therapy late

manifestations in untreated infants may

include central nervous system, skeletal,

and dental abnormalities hearing loss

and interstitial keratitis

Staphylococcal

pustulosis

Erythematous papules, pustules, honey-

colored crusts often in areas of trauma

Requires antibiotic therapy gram stain

and culture of lesions should be obtained

may be associated with systemic/invasive

infection

Staphylococcal

scalded skin

syndrome

(SSSS)

Fever, irritability, diffuse blanching

erythema, flaccid blisters positive

Nikolsky sign*

Requires antibiotic therapy cultures

should be obtained from any suspected

focus of infection (eg, blood, urine,

nasopharynx, umbilicus)

Streptococcal

infections

May mimic staphylococcal infections Same as for staphylococcal pustulosis and

SSSS

Listeria Pustules of the skin and mucus

membranes may be present in early

onset disease (


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congenita reepitheliaze to form hypertrophic or

atrophic scar involves the epidermis and

dermis

(eg, trisomy 13, 4p-)

Incontinentia

pigmenti

Four stages that may occur

simultaneously: linear streaks of

erythematous papules and vesicles warty

papules or plaques in linear or swirling

patterns swirled hypopigmented patches

or streaks

Majority of cases associated with

neurologic, ocular, dental, and structural

abnormalities

Miscellaneous

Scabies May be seen in infants as young as three

to four weeks of age, but never present at

birth vesicles, pustules, and papules, rare

burrows on hands, feet, trunk, genitalia

Requires treatment with scabicide and

measures to prevent spread

Cutaneous

mastocytosis

Bullous eruptions with hemorrhage

positive Darier sign

Requires symptomatic therapy and

avoidance of triggers

* Nikolsky sign: separation of the upper dermis and wrinkling of the skin with application of gentle pressure.

Darier sign: urticaria and erythema with rubbing, scratching, or stroking.

Graphic 75417 Version 3.0


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Clinical manifestations that are suggestive of specific congenital

infections in the neonate

Congenital

toxoplasmosis

Intracranial calcifications (diffuse)

Hydrocephalus

Chorioretinitis

Otherwise unexplained mononuclear CSF pleocytosis or elevated CSF protein

Congenital syphilis Skeletal abnormalities (osteochondritis and periostitis)

Pseudoparalysis

Persistent rhinitis

Maculopapular rash (particularly on palms and soles or in diaper area)

Congenital rubella Cataracts, congenital glaucoma, pigmentary retinopathy

Congenital heart disease (most commonly patent ductus arteriosus or peripheral

pulmonary artery stenosis)

Radiolucent bone disease

Sensorineural hearing loss

Congenital

cytomegalovirus

Thrombocytopenia

Periventricular intracranial calcifications

Microcephaly

Hepatosplenomegaly

Sensorineural hearing loss

Congenital herpes

simplex virus

Mucocutaneous vesicles or scarring

CSF pleocytosis

Thrombocytopenia

Elevated liver transaminases

Conjunctivitis or keratoconjuctivitis

Congenital varicella Cicatricial or vesicular skin lesions

Limb hypoplasia

CSF: cerebrospinal fluid.

Data from:

1. Maldonado YA, Nizet V, Klein JO, et al. Current concepts of infections of the fetus and newborn infant. In:

Infectious Diseases of the Fetus and Newborn Infant, 7th ed, Remington JS, Klein JO, Wilson CB, et al(Eds), Saunders, Philadelphia 2011. p.2.

2. Sanchez PJ, Demmler-Harrison GJ. Viral infections of the fetus and newborn. In: Feigin and Cherry's

Textbook of Pediatric Infectious Diseases, 6th ed. Feigin RD, Cherry JD, Demmler-Harrison GJ, Kaplan SL

(Eds), Saunders, Philadelphia 2009. p.895.

3. Stamos JK, Rowley AH. Timely diagnosis of congenital infections. Pediatr Clin North Am 1994 41:1017.



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Staphylococcal pustulosis

Community-associated Staphylococcus aureus pustulosis in the diaper area of a previously healthy

neonate.

Courtesy of Sheldon L Kaplan, MD



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Doses for antibiotics suggested in the treatment of suspected

staphylococcal skin and soft tissue infections in neonates

Parenteral

antibiotics

Infants 7 days of age Infants 8 to 28 days of age

BW 2 kg BW >2 kg BW 2 kg

Clindamycin 5 mg/kg IV

every 12 hours

5 mg/kg IV

every 8 hours

5 mg/kg IV

every 8 hours

5 mg/kg IV every 6 hours

Gentamicin* 5 mg/kg IV

every 48 hours

4 mg/kg IV

every 24 hours

5 mg/kg IV

every 36 hours

4 to 5 mg/kg IV every 24 hours

Lin ezolid 10 mg/kg IV

every 12 hours

10 mg/kg IV

every 8 hours

10 mg/kg IV

every 8 hours


Nafcillin 25 mg/kg IV

every 12 hours

25 mg/kg

every 8 hours

25 mg/kg IV

every 8 hours


Oxacillin 25 mg/kg IV

every 12 hours

25 mg/kg

every 8 hours

25 mg/kg IV

every 8 hours


Vancomycin Dosed according to serum creatinin e concen tration as indicated below

Serum creatinine concentration (mg/dL)

1.6

15 mg/kg IV

every 12 hours

20 mg/kg IV

every 24 hours

15 mg/kg IV

every 24 hours

10 mg/kg IV

every 24 hours

15 mg/kg IV

every 48 hours

Oral

antibiotics

Infants 7 days of age Infants 8 to 28 days of age

BW 2 kg BW >2 kg BW 2 kg

Cephalexin Oral therapy not appropriate 6.25 to 12.5 mg/kg orally every 6 hours

Clindamycin 5 mg/kg orallyevery 12 hours

5 mg/kg orallyevery 8 hours

5 mg/kg orallyevery 8 hours

5 mg/kg orally every 6 hours

Linezolid Oral therapy not appropriate 10 mg/kg orally

every 8 hours

10 mg/kg orally every 8 hours

BW: body weight IV: intravenously.

* Gentamicin is necessary to provide coverage for possible gram-negative pathogens. The optimal, individualized

dose should be based on determination of serum concentrations. Doses may differ from those recommended by

the package insert.

Dosing algorithm for vancomycin based upon serum creatinine concentration in neonates born at gestational

age >28 weeks. Serum creatinine concentration will take approximately 5 to 7 days after birth to reasonably

reflect neonatal renal function. Cautious use of creatinine-based dosing strategy with frequent assessment ofrenal function and vancomycin serum concentrations are recommended in neonates 7 days old . A

vancomycin dosing method based upon post-natal age and weight is provided as an alternative to the serum

creatinine-based method listed above and may be useful in some clinical situations. This particular algorithm was

provided in the 2009 edition of the Red Book .

Post-natal age


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Post-natal age 7 days:

2000 g: 10 to 15 mg/kg IV every 6 or 8 hours

Oral linezolid is reserved for isolates resistant to other agents and should be used under supervision by an

expert in infectious diseases.

References:1. Nelson's Pediatric Antimicrobial Therapy, 21st ed, Bradley JS, Nelson JD, Cantey JB, et al (Eds), American

Academy of Pediatrics, Elk Grove Village, IL 2015. p.36.

2. American Academy of Pediatrics. Antibacterial drugs for newborn infants: Dose and frequency of

administration. In: Red Book: 2009 Report of the Committee on Infectious Diseases, 28th ed, Pickering

LK (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2009. p.745.

Data adapted from: American Academy of Pediatrics. Tables of antibacterial drug dosages. In: Red Book: 2015

Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds),

American Academy of Pediatrics, Elk Grove Village, IL 2015. p.881.



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Contributor Disclosures

Sheldon L Kaplan, MD Grant/Research/Clinical Trial Support: Pfizer [S. pneumoniae (PCV13, Linezolid)] Cubist [S.aureus (Tedizolid)] Forest Lab [Osteomyelitis (Ceftaroline)]. Consultant/Advisory Boards: Pfizer [S. pneumoniae (PCV13,Linezolid) S. aureus (vaccine development)] Theravance [S. aureus (Telavancin)]. Morven S Edwards, MDGrant/Research/Clinical Trial Support: Pfizer Inc. [Group B Streptococcus]. Mary M Torchia, MD Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed byvetting through a multi-level review process, and through requirements for references to be provided to support the content.

Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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