Skin and soft tissue infections in neonates: Evaluation and management

INTRODUCTION — The evaluation and management of suspected Staphylococcus aureus or streptococcal skin and soft tissue infections (SSTIs) in neonates (≤28 days of age) are discussed here. Clinical features of SSTI; the evaluation and management of staphylococcal and streptococcal SSTIs in children older than 28 days; the epidemiology, prevention, and control of methicillin-resistant S. aureus (MRSA) infections in children; and the treatment of invasive MRSA infections in children are discussed separately.

●(See "Vesicular, pustular, and bullous lesions in the newborn and infant", section on 'Bacterial infection'.)

●(See "Erythroderma in children", section on 'Infectious diseases'.)

●(See "Skin and soft tissue infections in children >28 days: Evaluation and management".)

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

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

●(See "Staphylococcus aureus in children: Overview of treatment of invasive infections".)

ETIOLOGY — Most bacterial skin and soft tissue infections (SSTIs) in neonates are caused by S. aureus. Group B Streptococcus occasionally causes cellulitis. Group A streptococcal SSTIs in neonates are uncommon but may occur. (See "Vesicular, pustular, and bullous lesions in the newborn and infant", section on 'Bacterial infection' and "Erythroderma in children", section on 'Infectious diseases' and "Group B streptococcal infection in neonates and young infants", section on 'Other focal infection'.)

EVALUATION

History and examination — The clinical evaluation of the neonate with suspected bacterial skin and soft tissue infection (SSTI) focuses on identification of systemic infection and clinical manifestations of conditions that require management that differs from that of staphylococcal or streptococcal SSTI in neonates. These conditions often are associated with vesicopustular skin lesions (table 1). (See "Vesicular, pustular, and bullous lesions in the newborn and infant".)

Important aspects of the clinical evaluation include:

●Systemic signs or symptoms, such as fever (temperature ≥38°C [100.4°F]), hypothermia (temperature <35°C [95°F]), ill-appearance, irritability, and 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 neonates", section on 'Maternal risk factors' and "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Risk factors' and "Genital herpes simplex virus infection and pregnancy")

●Associated features of congenital HSV, neonatal varicella virus, or congenital syphilis (table 2) (see "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Neonatal HSV' and "Varicella-zoster infection in the newborn", section on 'Neonatal varicella' and "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis", section on 'Early congenital syphilis')

Laboratory evaluation

●Gram stain, culture, and susceptibility testing of purulent material – We obtain specimens for Gram stain, culture, and susceptibility testing from neonates with purulent/fluctuant skin lesions (ie, abscesses) if purulent material can be obtained [1-3].

Gram stain identification of gram-positive cocci may help to guide empiric therapy.

•Gram stain identification of gram-positive cocci in clusters provides early indication of staphylococcal infection. If S. aureus is isolated in bacterial culture, susceptibility testing is necessary to distinguish methicillin-resistant S. aureus from methicillin-susceptible S. aureus [4]. In some laboratories, methicillin resistance may be detected rapidly using commercially available molecular tests for the mecA gene that leads to methicillin resistance. (See "Rapid detection of methicillin-resistant Staphylococcus aureus".)

•Gram stain identification of gram-positive cocci in chains provides early identification of streptococcal infection. Culture is necessary to distinguish between group A and group B Streptococcus. The empiric treatment of neonatal group B streptococcal infection is discussed separately. (See "Group B streptococcal infection in neonates and young infants", section on 'Antimicrobial therapy'.)

●Other studies – Our approach to obtaining other laboratory studies and cultures in neonates with suspected bacterial SSTI depends upon the type of infection and associated systemic findings. Systemic findings include fever (temperature ≥38°C [100.4°F]), hypothermia (temperature <35°C [95°F]), ill-appearance, irritability, and poor feeding.

•Neonates with mastitis – The evaluation of neonates with mastitis is discussed separately. (See "Mastitis and breast abscess in infants younger than two months", section on 'Additional evaluation'.)

•Term neonates (≥37 weeks gestation) with localized pustulosis and no systemic findings – Localized pustulosis (picture 1) usually is caused by S. aureus. We generally do not obtain blood cultures or other microbiologic studies unless it is necessary to distinguish staphylococcal pustulosis from other causes of pustular lesions (table 1) [5]. In otherwise asymptomatic neonates with pustulosis, the Gram stain is helpful in distinguishing pustulosis from other conditions. If HSV remains a possibility, the infant should undergo full evaluation for HSV. (See "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Evaluation and diagnosis'.)

•Preterm (<37 weeks gestation), low birth weight neonates with localized pustulosis (with or without systemic findings) – We usually obtain blood cultures.

•Term or preterm neonates with multiple sites of pustulosis, other types of SSTI (eg, cellulitis, abscess, mastitis), or systemic findings – We obtain blood and urine cultures in all such patients and cerebrospinal fluid (CSF) cultures as clinically indicated (eg, fever/hypothermia, ill-appearing) [2]. Indications for CSF cultures in neonates are discussed separately:

-Preterm neonates (<34 weeks gestation) (see "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Other cultures')

-Term (>37 weeks gestation) and late preterm (34 to 36 weeks gestation) neonates <7 days (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Early-onset presentation')

-Term and late preterm neonates ≥7 days of age (see "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management", section on 'Focal infection' and "The febrile infant (29 to 90 days of age): Outpatient evaluation", section on 'Focal infection')

Significant CSF pleocytosis with sterile CSF culture may be seen in association with community-associated S. aureus infection in neonates [2,5]. The pathogenesis of the pleocytosis is unclear.

MANAGEMENT APPROACH

Localized pustulosis

●Term neonates without systemic findings – We suggest that localized pustulosis (picture 1) in term neonates (≥37 weeks gestation) without systemic findings (fever, hypothermia, ill-appearance, irritability, poor feeding) be treated with topical antibiotic therapy (eg, mupirocin three times daily for 5 to 10 days) in the outpatient setting (algorithm 1) [1,2]; close follow-up of such patients is imperative [2].

●Term neonates with systemic findings – We use parenteral rather than topical therapy for full-term neonates with localized pustulosis and fever or other signs or symptoms of systemic infection (algorithm 1). (See 'Choice of initial therapy' below.)

●Preterm (<37 weeks gestation) low birth weight neonates – We recommend that local pustulosis in preterm (<37 weeks gestation) low birth weight infants be treated parenterally at least until bacteremia is excluded (algorithm 1) [1]. If blood cultures were not obtained, a five- to seven-day course of parenteral therapy is reasonable – provided that the infant continues to be clinically well and the pustulosis resolved completely. (See 'Choice of initial therapy' below and 'Duration of therapy' below.)

SSTI more severe than localized pustulosis — We hospitalize neonates with skin and soft tissue infection (SSTI) more severe than localized pustulosis (eg, multiple sites of pustulosis, mastitis and other sites of cellulitis, abscess) for close monitoring and parenteral antimicrobial therapy (algorithm 1) [2]. In addition to provision of parenteral antimicrobial therapy, we recommend drainage of purulent or fluctuant lesions (eg, cutaneous abscess). (See 'Choice of initial therapy' below.)

Neonates with SSTI other than localized pustulosis are at increased risk for sepsis and invasive infection (given the immaturity of their immune system). (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates".)

Clinical features and clinical decision rules cannot accurately predict serious bacterial infection in young infants. Neonates with SSTI other than localized pustulosis 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.

ANTIMICROBIAL THERAPY — The safety and efficacy of topical, oral, and parenteral antimicrobial therapy for staphylococcal and streptococcal skin and soft tissue infection (SSTI) in neonates have not been well evaluated in clinical studies. We generally provide empiric coverage for S. aureus and add coverage for other pathogens as clinically indicated (algorithm 1).

Our approach to antimicrobial therapy is consistent with that provided by the Infectious Diseases Society of America [1], which is based upon observations from a review of 126 cases treated between 2001 and 2006 at the author's institution [2].

Choice of initial therapy — The empiric parenteral antibiotic regimen for suspected staphylococcal or streptococcal SSTI in neonates should be based upon the type of infection and local susceptibility pattern of community-associated S. aureus isolates. When the etiologic agent and susceptibility are known, antimicrobial therapy can be narrowed as indicated.

SSTI without systemic findings

●SSTI other than cellulitis – For neonates with SSTI other than cellulitis and no systemic findings (eg, fever, hypothermia, ill-appearance, irritability, poor feeding), we provide initial empiric coverage for methicillin-resistant S. aureus (MRSA) with vancomycin or clindamycin, given the high prevalence of MRSA in our community (algorithm 1 and table 3) [1,2]. For those infants in whom gram-negative pathogens are not a concern, monotherapy with linezolid or ceftaroline is an option in selected circumstances (eg, infection due to MRSA resistant to clindamycin in an infant with underlying renal dysfunction). Ceftaroline is available for infants born at ≥34 weeks' gestation and ≥12 days of age [6].

In communities where MRSA is less prevalent (eg, ≤15 percent of S. aureus isolates), initial empiric coverage for methicillin-susceptible S. aureus (MSSA) is an alternative (algorithm 1); other experts may have a different threshold of MRSA prevalence for MSSA coverage. Agents active against MSSA include nafcillin, oxacillin, or cefazolin; piperacillin-tazobactam is an alternative if it is necessary for another indication (eg, Pseudomonas) (table 3). Parenteral coverage should be broadened to include MRSA, group B Streptococcus (GBS), and enteric gram-negative pathogens if the infant develops systemic findings and to include MRSA, GBS, and other beta-hemolytic streptococci if the infant develops cellulitis. (See 'SSTI with systemic findings' below.)

Studies comparing antistaphylococcal regimens in neonates with SSTI are lacking. The antibiotics suggested above are equally reasonable based upon in vitro data and clinical observations.

●Cellulitis – For neonates with cellulitis and no systemic findings, we provide coverage for GBS and other beta-hemolytic streptococci in addition to MRSA (algorithm 1). Empiric parenteral therapy options include vancomycin plus either an extended spectrum cephalosporin (eg, cefotaxime [if available], ceftriaxone, ceftazidime) or gentamicin (table 3).

SSTI with systemic findings — For neonates with suspected staphylococcal or streptococcal infection who have systemic findings (eg, fever, hypothermia, ill-appearance, irritability, poor feeding) it is usually necessary to add coverage for other neonatal pathogens (ie, gentamicin, cefotaxime [if available], ceftazidime, cefepime, or ceftriaxone for enteric gram-negative pathogens) (algorithm 1). Ceftriaxone should be avoided in neonates with hyperbilirubinemia and in neonates receiving calcium-containing intravenous fluids. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Etiologic agents'.)

The combination of vancomycin plus one of these agents provides adequate empiric therapy for possible GBS cellulitis but is not appropriate for sepsis or meningitis (table 3). Appropriate antimicrobial regimens for neonatal sepsis and meningitis are discussed separately. (See "Management and outcome of sepsis in term and late preterm neonates", section on 'Initial empiric therapy' and "Group B streptococcal infection in neonates and young infants", section on 'Antimicrobial therapy'.)

Duration of therapy

●SSTI confined to the skin and soft tissues — The total duration of therapy for staphylococcal or streptococcal SSTI confined to the skin and soft tissues in neonates depends upon clinical response; a total of 7 to 14 days is usually adequate if there are no complications [2]. (See 'Response to therapy' below.)

For neonates with SSTI confined to the skin and soft tissues, we continue parenteral therapy at least until all of the following criteria are met (see 'Response to therapy' below):

•Resolution of systemic symptoms and fever

•Improvement in other clinical findings

•Antibiotic susceptibility results are available if a pathogen is isolated

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

Although we obtain blood cultures in preterm, low birth weight neonates with localized pustulosis, if blood cultures were not obtained, a five- to seven-day course of parenteral therapy is reasonable, provided that the infant continues to be clinically well and the pustulosis is completely resolved.

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 isolate (table 3) [7,8]. Oral linezolid may be used when the isolate is resistant to other agents, but, given its high cost, consultation with an expert in infectious diseases may be warranted to make sure that it is the only oral option [2]. If a pathogen is not isolated, we continue coverage with an oral agent with activity against both MRSA and MSSA (eg, clindamycin). Trimethoprim-sulfamethoxazole should not be used in neonates because it may displace bilirubin, increasing the risk for bilirubin toxicity.

●Invasive infection — The duration of antimicrobial therapy for neonates with staphylococcal or GBS infections that have extended beyond the skin and soft tissues is discussed separately. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Treatment of neonates' and "Group B streptococcal infection in neonates and young infants", section on 'Antimicrobial therapy'.)

RESPONSE TO THERAPY

Monitoring response — Response to therapy is indicated by clinical improvement after 48 hours. In neonates who are admitted to the hospital for antimicrobial therapy, we monitor the skin and soft tissue infection (SSTI) for improvement or progression, the patient's vital signs, and culture and susceptibility results (if obtained).

Neonates who are treated for staphylococcal or streptococcal SSTI in the outpatient setting should be instructed to seek medical care promptly if they develop systemic symptoms (eg, fever, hypothermia, irritability, ill-appearance, poor feeding) or if local symptoms worsen [9]. They should be seen for follow-up within 48 hours. Follow-up is essential to ensure clinical improvement and determine the need for drainage, additional drainage (if drained initially), 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) is indicated for neonates who worsen at any time during treatment and may be warranted for patients who remain stable but whose skin lesions have not 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.

In a retrospective study of 202 neonates treated with antibiotics for an uncomplicated SSTI, perirectal site of the infection was a risk factor for antibiotic treatment failure (17 percent with perirectal infections versus 5 percent with other types of infection [odds ratio 4.1, 95% CI 1.5-11.3]) [10].

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 methicillin-resistant S. aureus [MRSA] if MRSA was not initially included). In such cases, consultation with an expert in infectious diseases is suggested.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Skin and soft tissue infections".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th 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^th to 12^th 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 email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Methicillin-resistant Staphylococcus aureus (MRSA) (The Basics)")

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

SUMMARY AND RECOMMENDATIONS

●The clinical evaluation of the neonate with suspected Staphylococcus aureus or streptococcal skin and soft tissue infection (SSTI) focuses on identification of systemic infection and clinical manifestations of conditions that require management that differs from the management of staphylococcal or streptococcal SSTI in neonates. These conditions often are associated with vesicopustular skin lesions (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 bacterial SSTI depends upon the type of infection and associated clinical features. (See 'Laboratory evaluation' above.)

●For full term neonates with localized pustulosis (picture 1) and no systemic findings (eg, temperature ≥38°C [100.4°F] or <35°C [95°F], ill-appearance, irritability, poor feeding), we suggest topical rather than systemic therapy (algorithm 1) (Grade 2C). We generally use mupirocin three times daily for 5 to 10 days. Close outpatient follow-up is essential. (See 'Localized pustulosis' above.)

●We hospitalize preterm low birth weight neonates with localized pustulosis for parenteral therapy. We also hospitalize neonates with SSTI more severe than localized pustulosis (eg, pustulosis in multiple sites, cellulitis, abscess, mastitis) and neonates who undergo evaluation for serious bacterial infection (eg, bacteremia, urinary tract infection, meningitis, arthritis, osteomyelitis). (See 'Localized pustulosis' above and 'SSTI more severe than localized pustulosis' above.)

●The empiric parenteral antibiotic regimen for suspected staphylococcal or streptococcal SSTI in neonates should be based upon the type of infection and local susceptibility pattern of community-associated S. aureus isolates (algorithm 1). In areas with an increased prevalence of methicillin-resistant S. aureus, vancomycin, clindamycin, and linezolid or ceftaroline are appropriate alternatives for infection limited to the skin and soft tissues; gentamicin, cefotaxime (if available), ceftazidime, cefepime, or ceftriaxone may be added to broaden coverage (table 3). When the etiologic agent and susceptibility are known, antimicrobial therapy can be narrowed as indicated. (See 'Choice of initial therapy' above.)

●The duration of therapy for staphylococcal or streptococcal SSTI confined to the skin and soft tissues in neonates depends upon clinical response; a total of 7 to 14 days is usually adequate if there are no complications. (See 'Duration of therapy' above.)