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Management and outcome of sepsis in term and late preterm infants

Author: Morven S Edwards, MD

Section Editors: Leonard E Weisman, MD, Sheldon L Kaplan, MD
Deputy Editor: Carrie Armsby, MD, MPH

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Jul 31, 2017.

INTRODUCTION — Sepsis is an important cause of morbidity and mortality among newborn infants. Although
the incidence of sepsis in term and late preterm infants is low, the potential for serious adverse outcomes,
including death, is of such great consequence that caregivers should have a low threshold for evaluation and
treatment for possible sepsis in neonates. The approach discussed below is consistent with guidelines published
by the American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC) [1,2].

The treatment and outcome of sepsis in term and late preterm infants will be reviewed here. The epidemiology,
clinical features, diagnosis, and evaluation of sepsis in term and late preterm infants, neonatal sepsis in preterm
infants, the management of well-appearing infants at risk for group B streptococcal (GBS) infection, and the
evaluation of febrile or ill-appearing newborns are discussed separately:

● (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants".)

● (See "Clinical features and diagnosis of bacterial sepsis in the preterm infant (<34 weeks gestation)".)

● (See "Treatment and prevention of bacterial sepsis in the preterm infant (<34 weeks gestation)".)

● (See "Management of the infant whose mother has received group B streptococcal chemoprophylaxis".)

● (See "Febrile infant (younger than 90 days of age): Management", section on 'Neonates (28 days of age and
younger)'.)

● (See "Approach to the ill-appearing infant (younger than 90 days of age)".)

TERMINOLOGY — The following terms will be used throughout this discussion on neonatal sepsis:

● Neonatal sepsis is a clinical syndrome in an infant 28 days of life or younger, manifested by systemic signs
of infection and isolation of a bacterial pathogen from the bloodstream [3]. A consensus definition for
neonatal sepsis is lacking [4]. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late
preterm infants", section on 'Diagnosis'.)

● Term infants are those born at a gestational age of 37 weeks or greater.

● Late preterm infants (also called near-term infants) are those born from 34 through 36 completed weeks of
gestation [5]. (See "Late preterm infants".)

● Preterm infants are those born at less than 34 weeks of gestation [5].
Neonatal sepsis is classified according to the infant's age at the onset of symptoms:

● Early-onset sepsis is defined as the onset of symptoms before 7 days of age, although some experts limit
the definition to infections occurring within the first 72 hours of life [6].

● Late-onset sepsis is defined as the onset of symptoms at ≥7 days of age [6]. Similarly to early-onset
sepsis, there is variability in its definition, ranging from an onset at >72 hours of life to ≥7 days of age [6,7].

SUPPORTIVE CARE — Symptomatic infants should be treated in a care setting with full cardiopulmonary
monitoring and support, because the clinical course of these infants can deteriorate rapidly. Although there are
no data demonstrating the importance of supportive care measures in neonates with sepsis, it is generally
accepted that the following supportive measures are critical components of management:

● Maintaining adequate oxygenation and perfusion (see "Noninvasive oxygen delivery and oxygen monitoring
in the newborn")

● Prevention of hypoglycemia and metabolic acidosis (see "Management and outcome of neonatal
hypoglycemia")

● Maintenance of normal fluid and electrolyte status (see "Fluid and electrolyte therapy in newborns")

Severely ill patients may require ventilatory, volume, and/or vasopressor support to maintain adequate
oxygenation and perfusion. (See "Mechanical ventilation in neonates" and "Etiology, clinical manifestations,
evaluation, and management of neonatal shock".)

ONGOING DIAGNOSTIC EVALUATION

Other diagnostic considerations — In infants with suspected sepsis, additional testing for other conditions may
be warranted based on clinical signs and symptoms (table 1). It is often difficult to differentiate neonatal sepsis
from other diseases; however, given the morbidity and mortality of neonatal sepsis, empiric antibiotic therapy
should be provided (after cultures are obtained) to infants with suspected sepsis, pending definitive culture-
based diagnosis. Alternative diagnoses should be entertained when an infant with suspected sepsis has negative
cultures. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants", section on
'Differential diagnosis'.)

Lumbar puncture — If not done during the initial evaluation, a lumbar puncture (LP) should be performed in
infants, whenever possible, with culture-proven or culture-negative clinical sepsis. Clinical signs suggesting
meningitis can be lacking, and blood culture may be negative in infants with meningitis. (See "Bacterial
meningitis in the neonate: Clinical features and diagnosis".)

ANTIBIOTIC THERAPY

Whom to treat — The decision to start antibiotic therapy is based on assessment of risk factors, clinical
evaluation, and laboratory tests. Indications for empiric antibiotic therapy include (see "Clinical features,
evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Evaluation and initial
management'):

● Ill-appearance (see "Approach to the ill-appearing infant (younger than 90 days of age)")

● Concerning symptoms, including temperature instability, or respiratory, cardiocirculatory, or neurologic

symptoms (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants",
section on 'Clinical manifestations')
 ● Cerebrospinal fluid (CSF) pleocytosis (white blood cell [WBC] cell count of >20 to 30 cells/microL) (table 2)
(see "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on 'Interpretation of CSF')

● Confirmed or suspected maternal chorioamnionitis (see "Clinical features, evaluation, and diagnosis of
sepsis in term and late preterm infants", section on 'Maternal risk factors')

● Positive blood, urine, or CSF culture (see "Clinical features, evaluation, and diagnosis of sepsis in term and
late preterm infants", section on 'Blood culture')

Initial empiric therapy — The initial choice of parenteral antimicrobials for suspected sepsis in term and late
preterm neonates is based on the infant's age, likely pathogens, the susceptibility patterns of organisms in a
particular nursery, and the presence of an apparent source of infection (eg, skin, joint, or bone involvement)
(table 3).

Early-onset sepsis — The recommended empiric regimen for suspected early-onset sepsis in a term or late
preterm infant is ampicillin 150 mg/kg per dose intravenously (IV) every 12 hours and gentamicin 4 mg/kg per
dose IV every 24 hours [7,8]. We generally obtain baseline renal function tests (ie, blood urea nitrogen and
creatinine levels) at the initiation of treatment with gentamicin. Serum gentamicin levels should be obtained in
infants receiving a full course of antibiotics but are not required if a treatment course of only 48 hours is
anticipated and renal function is normal [3,7].

The combination of ampicillin and gentamicin is effective in treating most common pathogens that cause early-
onset sepsis, including group B Streptococcus (GBS), Listeria, Enterococcus, and most isolates of Escherichia
coli (table 4) [1,9].

In a national surveillance study (2006 to 2008), 94 percent of all isolates in neonates were susceptible to the
combination of penicillin and gentamicin [10]. In a 10-year review from a single center, 90 percent of early-onset
sepsis pathogens in term and late preterm infants were susceptible to ampicillin and/or gentamicin [11]. Among
six infants with early-onset Staphylococcus aureus bacteremia that was not susceptible to ampicillin and
gentamicin, there were no complications before or after antibiotic therapy was adjusted, based upon antibiotic
susceptibility.

Ampicillin and gentamicin are preferred over ampicillin and a third-generation cephalosporin (eg, cefotaxime),
based upon the following:

● The regimen of ampicillin and a third-generation cephalosporin is not more effective than the combination of
ampicillin and gentamicin [12].

● The emergence of cephalosporin-resistant gram-negative organisms (eg, Enterobacter cloacae, Klebsiella,

and Serratia species) can occur when cefotaxime is used routinely [1,13].

● Ampicillin and gentamicin are synergistic in treating infections caused by GBS and Listeria monocytogenes.
Cephalosporins are not active against L. monocytogenes.

● In a large cohort study, infants who received ampicillin plus cefotaxime had a 1.5-fold increase in mortality
compared with those treated with ampicillin plus gentamicin (4.2 versus 1.9 percent, adjusted odds ratio
[OR] 1.5, 95% CI 1.4-1.7) [12].

● Ceftriaxone is highly bound to albumin and appears to displace bilirubin [14,15]. Although displacement of
free bilirubin by ceftriaxone has not been reported, avoidance of ceftriaxone in neonates at risk for acute
bilirubin encephalopathy is recommended [1].
The addition of a third-generation cephalosporin to the regimen of ampicillin and gentamicin is warranted for
infants with suspected meningitis and critically ill neonates with risk factors associated with ampicillin-resistant
infections (ie, prolonged rupture of membranes and/or prolonged antenatal maternal ampicillin treatment).

Late-onset sepsis — The choice of empiric therapy for late-onset sepsis depends upon whether the infant is
admitted from the community and thus is at lower risk for infection caused by a multidrug-resistant pathogen or is
hospitalized since birth and thus at a higher risk.

Admitted from the community — Neonates admitted from the community are at lower risk for infection
caused by a multidrug-resistant pathogen than are infants who remain hospitalized since birth. The combination
of ampicillin and gentamicin or ampicillin and a third-generation cephalosporin (eg, cefotaxime, if available) are
regimens for empiric treatment of sepsis without an apparent focus of infection in this setting (table 3) [6].

Ampicillin and gentamicin is generally the preferred regimen; however, local antibiotic resistance patterns must
be considered. The dosing for ampicillin is 75 mg/kg per dose IV every six hours; the dosing of gentamicin is 4
mg/kg per dose IV every 24 hours [7,8]. We generally obtain baseline renal function tests (ie, blood urea nitrogen
and creatinine levels) at the initiation of treatment with gentamicin. Serum gentamicin levels should be obtained
in infants receiving a full course of antibiotics but are not required if a treatment course of only 48 hours is
anticipated and renal function is normal [3,7].

In a national surveillance study (2006 to 2008), 96 percent of isolates from late-onset bacteremia were
susceptible to the combination of amoxicillin and gentamicin [10]. The addition of a third-generation
cephalosporin to an ampicillin and gentamicin regimen is warranted for neonates with suspected meningitis. (See
'Special circumstances' below.)

Hospitalized since birth — Infants who continue to be hospitalized since birth are at higher risk for
multidrug-resistant organisms, and therefore, vancomycin is substituted for ampicillin (table 3). For term infants
>7 days of life, the dosing of vancomycin is dependent on serum creatinine (Scr) [16]:

● Scr <0.7 mg/dL – 15 mg/kg/dose IV every 12 hours

● Scr 0.7 to 0.9 mg/dL – 20 mg/kg/dose IV every 24 hours

● Scr 1 to 1.2 mg/dL – 15 mg/kg/dose IV every 24 hours

● Scr 1.3 to 1.6 mg/dL – 10 mg/kg/dose IV every 24 hours

● Scr >1.6 mg/dL – 15 mg/kg/dose IV every 48 hours

Alternative weight-directed neonatal dosing recommendations for vancomycin in are also available (refer to
Lexicomp pediatric drug information).

Special circumstances — Alternative regimens based upon specific clinical circumstances include the
following (table 3):

● Suspected meningitis – In neonates with late-onset sepsis in whom the lumbar puncture (LP) suggests
meningitis (eg, CSF pleocytosis), a third-generation cephalosporin (eg, cefotaxime, if available) should be
included in the regimen. Cefotaxime should also be added to the empiric regimen for early-onset meningitis
if the CSF Gram stain reveals gram-negative bacilli. Cefotaxime provides extended spectrum for enteric
gram-negative rods and has optimal activity in the CSF against pneumococci. If cefotaxime is not available,
alternative agents include ceftazidime, ceftriaxone (not to be used in infants with clinically significant
hyperbilirubinemia or those receiving concurrent IV calcium [including parenteral nutrition]), or meropenem.
Meropenem is preferred if there is concern for infection due to a multidrug-resistant gram-negative
 organism. Treatment of bacterial meningitis in neonates is discussed in detail separately. (See "Bacterial
meningitis in the neonate: Treatment and outcome", section on 'Empiric therapy'.)

● Suspected pneumonia − Empiric regimens for treatment of infants with a pulmonary focus of infection
include ampicillin and gentamicin, ampicillin and a third-generation cephalosporin (eg, cefotaxime, if
available), vancomycin and cefotaxime (if available), or vancomycin and gentamicin. Treatment of
pneumonia in neonates is discussed in detail separately. (See "Neonatal pneumonia", section on
'Treatment'.)

● Skin, soft tissue, bone, and joint infections – If there is a focus of infection involving the skin, soft tissues,
bone, or joints (in which case S. aureus is a likely pathogen), vancomycin should be substituted for ampicillin
[17]. In a toxic-appearing infant, nafcillin should also be added.

● Catheter-related infection – If intravascular catheter-related infection is a concern, treatment should be

initiated with vancomycin and gentamicin to provide empiric coverage for coagulase-negative staphylococci,
S. aureus, and gram-negative bacteria.

● Suspected intestinal source – If infection is thought to arise from the gastrointestinal tract (eg, anaerobic
bacteria), clindamycin or another suitable agent, such as metronidazole, should be added to the therapeutic
regimen to improve coverage for these pathogens.

Culture-proven sepsis — In neonates with culture-proven sepsis, the usual course of therapy is 10 days
[1,3,13,18,19]. Longer treatment courses may be warranted if a specific focus of infection is identified (eg,
meningitis, osteomyelitis, or septic arthritis). Antimicrobial therapy should be altered based upon the
susceptibility profile of the pathogen isolated.

Pathogen-specific therapy — For the most common causative organisms of neonatal sepsis, antimicrobial
therapy is as follows (table 3):

Group B Streptococcus — The drug of choice for group B Streptococcus (GBS) is penicillin. Thus, when
GBS is identified and resolution of bacteremia is documented by a repeat blood culture and in infants with
meningitis the CSF is sterile, we recommend discontinuing gentamicin and continuing therapy with penicillin G
alone (table 5). (See "Group B streptococcal infection in neonates and young infants", section on 'Definitive
therapy'.)

Escherichia coli — In patients with ampicillin-sensitive Escherichia coli (E. coli) sepsis who have
improved clinically and in whom meningitis has been excluded, ampicillin monotherapy is administered for a 10-
day course.

For patients with ampicillin-resistant E. coli, the choice of definitive therapy is based upon the susceptibility
profile. Cefotaxime (if available) is often employed if the isolate is susceptible.

Other gram-negative bacilli — Antimicrobial treatment of infections caused by Klebsiella, Proteus,

Enterobacter, Serratia, Pseudomonas, Salmonella, or Shigella should be selected based upon the susceptibility
profile of the organism. Single-agent therapy is sufficient in most cases.

Infections caused by multidrug-resistant, gram-negative bacilli, including those caused by extended-spectrum

beta-lactamase-producing organisms or those with hyperproduction of beta-lactamases, should be treated with
meropenem.

Listeria monocytogenes — The combination of ampicillin and gentamicin is used for initial therapy.
Treatment with both agents is more effective than ampicillin alone in vitro and in animal models of Listeria
infection. Cephalosporins are not active against L. monocytogenes. Duration of therapy usually is 10 days. (See
"Treatment, prognosis, and prevention of Listeria monocytogenes infection", section on 'Antibiotic regimens'.)

Staphylococcus species — Directed therapy for infection caused by staphylococci is determined by the
sensitivity of the isolate to specific antibiotic agents:

● Staphylococcus aureus – Vancomycin, or in a toxic-appearing infant, vancomycin plus nafcillin, should be

employed for S. aureus infection until the susceptibility profile is available. The regimen then should be
adjusted according to the susceptibility profile:

• Methicillin-susceptible S. aureus (MSSA) – Treatment of MSSA infection should be completed with

nafcillin. Cefazolin is an alternative for treatment of most MSSA infections outside the central nervous
system (CNS) and not involving endocarditis. (See "Staphylococcus aureus bacteremia in children:
Management and outcome".)

• Methicillin-resistant S. aureus (MRSA) – Treatment should be completed with vancomycin. (See

"Methicillin-resistant Staphylococcus aureus in children: Treatment of invasive infections", section on
'Treatment of neonates'.)

● Coagulase-negative staphylococci – Coagulase-negative staphylococcal infections require treatment with

vancomycin.

Probable but unproven sepsis — In infants with a negative blood culture but a clinical status that remains
concerning for a systemic infection (eg, ongoing temperature instability; ongoing respiratory, cardiocirculatory, or
neurologic symptoms not explained by other conditions; or laboratory abnormalities suggestive of sepsis),
antibiotic therapy can be extended for as long as a total of 5 to 10 days.

After 48 hours, the empiric regimen is altered based upon whether or not meningitis has been excluded:

● If meningitis has been excluded, the ampicillin regimen can be changed to 75 mg/kg every 12 hours.

● If LP has not been performed, ampicillin should be continued at a meningitic dose.

● Management of infants with CSF pleocytosis and/or positive CSF culture is discussed separately. (See
"Bacterial meningitis in the neonate: Treatment and outcome".)

Alternative diagnoses should also be entertained when an infant with suspected sepsis has negative cultures
(table 1). Antibiotics should be discontinued when another diagnosis is established. (See "Clinical features,
evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Differential diagnosis'.)

Infection unlikely — Empiric antibiotics are initiated in many infants with maternal risk factors, abnormal
laboratory values, and/or mild-to-moderate symptoms that subsequently resolve. Sepsis is unlikely in these
infants if they remain well and the blood culture is sterile at 48 hours. Empiric antibiotic therapy should be
discontinued after 48 hours in these neonates [1,20].

Response to therapy — In most cases, symptomatic infants with proven sepsis improve clinically within 24 to
48 hours.

In infants with bacteremia, a repeat blood culture should be obtained after 24 to 48 hours of therapy to document
sterility. Failure to sterilize the bloodstream suggests that the antimicrobial(s) chosen are not active against the
infecting pathogen or that there is an unrecognized focus of infection. Consultation with a pediatric infectious
disease specialist may be warranted.
ADJUNCTIVE THERAPIES — The following adjunctive immunotherapeutic interventions have been studied in
neonatal sepsis, but should not be routinely administered, as they have not been shown to conclusively improve
outcomes [18,19,21]:

● Intravenous immunoglobulin (IVIG) infusions [22,23]

● Granulocyte transfusions [24]

● Granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) [25,26]

● Pentoxifylline [27]

● Lactoferrin [28]

PREVENTION — The primary intervention to prevent neonatal sepsis is the use of intrapartum antibiotic
prophylaxis (IAP) in mothers with group B streptococcal (GBS) colonization and other risk factors. Although IAP
has resulted in a decrease in the incidence of early-onset GBS invasive neonatal infection, it has not had a
similar impact on the rate of late-onset GBS disease. (See "Neonatal group B streptococcal disease: Prevention"
and "Group B streptococcal infection in neonates and young infants", section on 'Epidemiology'.)

Comprehensive prevention of neonatal sepsis will require a multi-interventional program including effective
maternal vaccination, reduction in preterm delivery, and limited exposure of term infants to potential pathogens.
(See "Vaccines for the prevention of group B streptococcal disease".)

OUTCOME — Overall mortality in term and late preterm infants with neonatal sepsis is approximately 2 to 4
percent [12,29]. Mortality estimates vary depending on gestational age of the infant (lower gestational age is
associated with higher mortality), pathogen (E. coli is associated with higher mortality than GBS), and sepsis
definition (lower mortality rates tend to be reported if infants with culture-negative clinical sepsis are included
compared with cases of culture-proven sepsis only).

Mortality rates for GBS sepsis in term infants after the introduction of IAP and routine use of empirical antibiotic
therapy range from 2 to 3 percent for early-onset disease and 1 to 2 percent for late-onset disease. The risk of
mortality is higher in infants with birth weight less than 2500 g, absolute neutrophil count less than 1500
cells/microL, hypotension, apnea, and pleural effusion [30]. (See "Group B streptococcal infection in neonates
and young infants", section on 'Outcome'.)

The risk of mortality is particularly high in neonates with early-onset sepsis caused by E. coli. Estimated mortality
rates for term neonates with E. coli sepsis are 6 to 10 percent [9,29,31].

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: Sepsis in neonates" and
"Society guideline links: Group B streptococcal infection in pregnant women and neonates".)

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"Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
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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
"patient info" and the keyword(s) of interest.)

● Basics topics (see "Patient education: Sepsis in newborn babies (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Although the incidence of sepsis in term and late preterm infants is low, the potential for serious adverse
outcomes, including death, is of such great consequence that caregivers should have a low threshold for
evaluation and treatment for possible sepsis. (See 'Introduction' above.)

● Supportive care for symptomatic infants is delivered in an intensive care setting to ensure adequate
oxygenation, perfusion, and maintenance of normal fluid and electrolyte balance, especially in severely
affected patients. (See 'Supportive care' above.)

● Indications for empiric antibiotic therapy include any of the following:

• Ill-appearance (see "Approach to the ill-appearing infant (younger than 90 days of age)")

• Concerning symptoms, including temperature instability or respiratory, cardiocirculatory, or neurologic

symptoms (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants",
section on 'Clinical manifestations')

• Cerebrospinal fluid (CSF) pleocytosis (white blood cell [WBC] cell count of >20 to 30 cells/microL) (table
2) (see "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on 'Interpretation
of CSF')

• Confirmed or suspected maternal chorioamnionitis (see "Clinical features, evaluation, and diagnosis of
sepsis in term and late preterm infants", section on 'Maternal risk factors')

• Positive blood, urine, or CSF culture (see "Clinical features, evaluation, and diagnosis of sepsis in term
and late preterm infants", section on 'Blood culture')

● We recommend suspected neonatal sepsis be treated initially with empiric antibiotic therapy (table 3) that
provides broad coverage for the most likely pathogens (group B Streptococcus [GBS] and gram-negative
enteric organisms, including Escherichia coli [E. coli]) (table 4) (Grade 1B).

• For neonates with early-onset sepsis without an apparent focus, we suggest initial empiric therapy
with ampicillin and gentamicin rather than other agents (Grade 2C). (See 'Early-onset sepsis' above.)

• For neonates with late-onset sepsis without an apparent focus, we suggest the following (see 'Late-
onset sepsis' above):

- For neonates admitted from the community, we suggest ampicillin and gentamicin rather than other
agents (Grade 2C).

- For infants who continue to be hospitalized from birth, we suggest vancomycin and gentamicin
rather than other agents (Grade 2C).

• If the clinical findings suggest a focal source of infection, the empiric antibiotic regimen is modified as
follows (table 3) (see 'Special circumstances' above):

- If there is concern of late-onset meningitis, a third-generation cephalosporin (eg, cefotaxime, if

available) is added to the regimen. (See "Bacterial meningitis in the neonate: Treatment and
outcome", section on 'Empiric therapy'.)
 - If there is concern for pneumonia, acceptable empiric regimens include ampicillin and gentamicin,
ampicillin and a third-generation cephalosporin (eg, cefotaxime, if available), vancomycin and
cefotaxime (if available), or vancomycin and gentamicin. (See "Neonatal pneumonia", section on
'Treatment'.)

- If there is a focus of infection involving the skin, soft tissues, bone, or joints, vancomycin is
substituted for ampicillin (in toxic-appearing infants, nafcillin is also added).

- If intravascular catheter-related infection is a concern, the empiric regimen consists of vancomycin

and gentamicin.

- If an intestinal source for sepsis is suspected, clindamycin or metronidazole is added to the

regimen.

● Antibiotic therapy is altered based upon isolation of the causative agent and its antimicrobial susceptibility
pattern. (See 'Pathogen-specific therapy' above.)

● In infants with culture-proven sepsis, the usual course of therapy is 10 days. Longer treatment is warranted if
a specific focus of infection is identified (eg, meningitis, osteomyelitis, or septic arthritis). (See 'Culture-
proven sepsis' above.)

● In well-appearing infants with negative cultures after 48 hours, empiric antibiotic therapy should be
discontinued, as sepsis is unlikely in these infants. (See 'Infection unlikely' above.)

● Most infants with culture-proven sepsis improve clinically within 24 to 48 hours after appropriate antibiotic
treatment is started. The response to antibiotic therapy is assessed by a repeat blood culture 24 to 48 hours
after initiation of antibiotic therapy. Failure to sterilize the bloodstream suggests either that the
antimicrobial(s) chosen are not active against the infecting pathogen or that there is an unrecognized focus
of infection. (See 'Response to therapy' above.)

● The mortality of neonatal sepsis in term infants is less than 10 percent. (See 'Outcome' above.)

● The primary intervention to prevent neonatal sepsis is the use of intrapartum antibiotic prophylaxis (IAP) in
mothers with documented GBS colonization, a previous birth of an infant with GBS disease, or GBS
bacteriuria during the current pregnancy. (See "Neonatal group B streptococcal disease: Prevention".)

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21. Cohen-Wolkowiez M, Benjamin DK Jr, Capparelli E. Immunotherapy in neonatal sepsis: advances in
treatment and prophylaxis. Curr Opin Pediatr 2009; 21:177.
22. INIS Collaborative Group, Brocklehurst P, Farrell B, et al. Treatment of neonatal sepsis with intravenous
immune globulin. N Engl J Med 2011; 365:1201.
23. Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or proven infection in neonates. Cochrane
Database Syst Rev 2015; :CD001239.
 24. Pammi M, Brocklehurst P. Granulocyte transfusions for neonates with confirmed or suspected sepsis and
neutropenia. Cochrane Database Syst Rev 2011; :CD003956.
25. Schibler KR, Osborne KA, Leung LY, et al. A randomized, placebo-controlled trial of granulocyte colony-
stimulating factor administration to newborn infants with neutropenia and clinical signs of early-onset
sepsis. Pediatrics 1998; 102:6.
26. Carr R, Modi N, Doré C. G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane
Database Syst Rev 2003; :CD003066.
27. Pammi M, Haque KN. Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates.
Cochrane Database Syst Rev 2015; :CD004205.
28. Pammi M, Suresh G. Enteral lactoferrin supplementation for prevention of sepsis and necrotizing
enterocolitis in preterm infants. Cochrane Database Syst Rev 2017; 6:CD007137.
29. Weston EJ, Pondo T, Lewis MM, et al. The burden of invasive early-onset neonatal sepsis in the United
States, 2005-2008. Pediatr Infect Dis J 2011; 30:937.
30. Payne NR, Burke BA, Day DL, et al. Correlation of clinical and pathologic findings in early onset neonatal
group B streptococcal infection with disease severity and prediction of outcome. Pediatr Infect Dis J 1988;
7:836.
31. Escobar GJ, Li DK, Armstrong MA, et al. Neonatal sepsis workups in infants >/=2000 grams at birth: A
population-based study. Pediatrics 2000; 106:256.

Topic 5046 Version 31.0

GRAPHICS

Differential diagnosis of neonatal sepsis

Diagnosis Distinguishing features Diagnostic tests

Other systemic neonatal infections

Viral infections:

Herpes simplex virus Mucocutaneous vesicles, CSF Viral culture; HSV PCR
pleocytosis, elevated CSF protein,
thrombocytopenia, hepatitis

Enteroviruses Fulminant systemic disease, Viral culture; EV PCR

myocarditis, hepatitis, encephalitis

Parechovirus Encephalitis/meningitis, rash on palms HPeV PCR (available through CDC)

and soles

Cytomegalovirus Thrombocytopenia, periventricular Viral culture; CMV PCR

intracranial calcifications,
microcephaly, sensorineural hearing
loss, chorioretinitis

Influenza viruses Respiratory symptoms, rhinorrhea, Viral culture; influenza-specific

gastrointestinal symptoms antigen detection or
immunofluorescence assay

Respiratory syncytial virus Respiratory symptoms, rhinorrhea, Viral culture; RSV-specific antigen
cough, apnea, pneumonia detection or immunofluorescence
assay

Spirochetal infections – Syphilis Skeletal abnormalities RPR or VDRL

(osteochondritis and periostitis),
pseudoparalysis, persistent rhinitis,
maculopapular rash (particularly on
palms and soles or in diaper area)

Parasitic infections:

Congenital malaria Anemia, splenomegaly, jaundice Detection of parasitemia on blood

smear

Toxoplasmosis Intracranial calcifications (diffuse), Toxoplasma gondii serology

hydrocephalus, chorioretinitis,
mononuclear CSF pleocytosis,
elevated CSF protein

Fungal infection – Candidiasis Persistent hyperglycemia, Isolation of Candida in blood, urine, or

thrombocytopenia, multiorgan failure CSF culture

Noninfectious causes of temperature instability in neonates

Altered environmental temperature Transient; no other systemic symptoms; resolves with simple
nonpharmacologic measures

Dehydration Clinical history of poor feeding or fluid losses (eg, vomiting and/or diarrhea)

Neonatal abstinence syndrome History of maternal drug use; Positive drug screening tests
sweating, sneezing, nasal stuffiness,
and yawning

CNS insult (eg, anoxia or History of perinatal asphyxia; focal Abnormal neuroimaging studies
hemorrhage) neurologic findings or seizures

Hypothyroidism Hypotonia, lethargy, hypothermia, Abnormal T4 or TSH level on newborn

large fontanels screen

Congenital adrenal hyperplasia Ambiguous genitalia (females), Abnormal 17a-hydroxyprogesterone


Noninfectious causes of respiratory and cardiocirculatory symptoms in neonates
Transient tachypnea of the newborn
Respiratory distress syndrome
Meconium aspiration
Pneumothorax
Congenital anomalies (including
tracheal-esophageal fistula, choanal
atresia, and diaphragmatic hernia)
Neonatal abstinence syndrome
Cardiac arrhythmias (eg,
supraventricular tachycardia)
Congenital heart disease
Noninfectious causes of neurologic symptoms in neonates
Hypoglycemia
Hypercalcemia
Hypermagnesemia
CNS insult (eg, anoxia or
hemorrhage)
Congenital CNS malformations (eg,
adrenal insufficiency and salt-wasting
(hyponatremia, hyperkalemia,
dehydration)
Onset of symptoms within two hours
after delivery; symptoms usually
resolve within 24 hours
Most common in preterm infants; rare
in term infants; onset of symptoms
within first few hours after delivery,
progressively worsens over first 48
hours of life
History of meconium-stained amniotic
fluid; respiratory distress occurs
immediately after birth
Asymmetric chest rise, decreased
breath sounds on affected side;
hypotension (in cases of tension
pneumothorax)
Often occur with other congenital
anomalies including VACTERL and
CHARGE associations; choanal atresia
is characterized by noisy labored
breathing while feeding
History of maternal drug use;
sweating, sneezing, nasal stuffiness,
and yawning
Abrupt onset and termination of rapid
heart rate
Infants with ductal-dependent lesions
may initially lack symptoms then
develop cyanosis and rapid clinical
deterioration as the PDA closes in the
first few days of life
Common in infants who are large for
gestational age and/or infants of
diabetic mothers
Increased neuromuscular irritability
and seizures; associated with
prematurity, maternal diabetes, and
perinatal asphyxia
Generalized hypotonia, respiratory
depression and apnea; typically
results from maternal treatment with
magnesium sulfate
History of perinatal asphyxia; focal
neurologic findings or seizures
Abnormal head circumference
level on newborn screen
CXR findings include increased lung
volumes, mild cardiomegaly,
prominent vascular markings, fluid in
the interlobar fissures, and pleural
effusions
CXR findings include low lung volume
and diffuse reticulogranular ground
glass appearance with air
bronchograms
Initial CXR may show streaky, linear
densities; as the disease progresses,
the lungs may appear hyperinflated
with diffuse patchy densities
CXR will usually detect symptomatic
pneumothoraces
CDH is often diagnosed by routine
antenatal ultrasound screening;
postnatal CXR shows herniation of
abdominal contents into hemithorax;
TEF is diagnosed with upper
gastrointestinal series and/or
bronchoscopy
Positive drug screening tests
Abnormal ECG
Abnormal hyperoxia test; abnormal
echocardiography
Abnormal blood glucose level
Abnormal serum calcium level
Abnormal serum magnesium level
Abnormal neuroimaging studies
Abnormal neuroimaging studies
 hydrocephalus)

Neonatal abstinence syndrome History of maternal drug use; Positive drug screening tests
sweating, sneezing, nasal stuffiness,
and yawning

Inborn errors of metabolism
Otherwise unexplained acid-base Positive newborn screen for inborn
disorders, hyperammonemia, errors of metabolism
hypoglycemia, hematologic
abnormalities, liver dysfunction, and
renal disease

Pyridoxine deficiency Refractory seizures Abnormal plasma pyridoxal-5-

phophate level

CSF: cerebral spinal fluid; HSV: herpes simplex virus; PCR: polymerase chain reaction; EV: enterovirus; HPeV: human
parechovirus; CMV: cytomegalovirus; RSV: respiratory syncytial virus; RPR: rapid plasma reagin; VDRL: venereal disease
research laboratory; CNS: central nervous system; T4: thyroxine; TSH: thyrotropin; CXR: chest radiograph; CDH: congenital
diaphragmatic hernia; VACTERL: malformations of the vertebrae, anus, cardiac structures, trachea, esophagus, renal system,
and limbs; CHARGE: coloboma of the iris or choroid, heart defect, atresia of the choanae, retarded growth and development,
genitourinary abnormalities, and ear defects; TEF: tracheoesophageal fistula; ECG: electrocardiogram; PDA: patent ductus
arteriosus.

Adapted from: Nizet V, Klein JO. Bacterial sepsis and meningitis. In: Infectious diseases of the fetus and newborn infant, 7 th
ed, Remington JS, et al (Eds), Elsevier Saunders, Philadelphia 2010.

Graphic 100409 Version 2.0

Characteristics of cerebrospinal fluid in term and preterm neonates without
bacterial meningitis

Mean
ANC/mm 3 or Mean protein Mean glucose
WBC/mm 3
Age percent PMNs (mg/dL) (mg/dL)
(range or 90th
(range) (range or ±SD) (range or ±SD)
percentile)

Term neonates evaluated in the nursery setting

0 to 24 hours 5 (0 to 90) 3/mm 3 (0 to 70) 63 (32 to 240) 51 (32 to 78)

(n = 135)* [1]

0 to 10 days 8.2 (0 to 32) 61.3 percent 90 (20 to 170) 52 (34 to 119)

(n = 87) ¶[2]

0 to 32 days 11 (1 to 38) 21 percent (0 to 100) NR NR

(n = 24) ¶[3]

Term neonates evaluated in the emergency department setting Δ

0 to 7 days 15.3 (1 to 130) 4.4/mm 3 (0 to 65) 80.8 (±30.8) 45.9 (±7.5)

(n = 17) [4]

0 to 7 days 8.6 (90 th percentile: NR 106.4 (90 th NR

(n = 118) [5] 26) percentile: 153)

1 to 28 days 6.1 (0 to 18) NR 75.4 (15.8 to 131) 45.3 (30 to 61)

(n = 297) [6]

0 to 30 days 7.3 (0 to 130) ◊ 0.8/mm 3 (0 to 65) 64.2 (±24.2) 51.2 (±12.9)

(n = 108) [4]

8 to 14 days 3.9 (90 th percentile: NR 77.6 (90 th percentile: NR

(n = 101) [5] 9) 103)

8 to 14 days 5.4 (0 to 18) 0.1/mm 3 (0 to 1) 69 (±22.6) 54.3 (±17)

(n = 33) [4]

15 to 22 days 4.9 (90 th percentile: NR 71 (90 th percentile: NR

(n = 107) [5] 9) 106)

15 to 21 days 7.7 (0 to 62) 0.2/mm 3 (0 to 2) 59.8 (±23.4) 46.8 (±8.8)

(n = 25) [4]

22 to 28 days 4.5 (90 th percentile: NR 68.7 (90 th percentile: NR

(n = 141) [5] 9) 85)

22 to 30 days 4.8 (0 to 18) 0.1/mm 3 (0 to 1) 54.1 (±16.2) 54.1 (±16.2)

(n = 33) [4]

Preterm or low birth weight neonates

0 to 28 days 9 (0 to 29) 57.2 percent 115 (65 to 150) 50 (24 to 63)

(n = 30 §) ¶[2]

0 to 32 days 7 (0 to 28) 16 percent (0 to 100) NR NR

(n = 22 ¥) ¶[3]

Very low birth weight neonates [7]

<1000 g

0 to 7 days 3 (1 to 8) 11 percent (0 to 50) 162 (115 to 222) 70 (41 to 89)

(n = 6)

8 to 28 days 4 (0 to 14) 8 percent (0 to 66) 159 (95 to 370) 68 (33 to 217)

(n = 17)

29 to 84 days 4 (0 to 11) 2 percent (0 to 36) 137 (76 to 269) 49 (29 to 90)

(n = 15)
 1000 to 1500 g

0 to 7 days 4 (1 to 10) 4 percent (0 to 28) 136 (85 to 176) 74 (50 to 96)

(n = 8)

8 to 28 days 7 (0 to 44) 10 percent (0 to 60) 137 (54 to 227) 59 (39 to 109)

(n = 14)

29 to 84 days 8 (0 to 23) 11 percent (0 to 48) 122 (45 to 187) 47 (31 to 76)

(n = 11)

WBC: white blood cell count; ANC: absolute neutrophil count; PMNs: polymorphonuclear leukocytes; SD: standard deviation;
NR: not reported; CSF: cerebrospinal fluid.
* CSF obtained from term neonates without any obvious pathology.
¶ CSF obtained from hospitalized neonates at high risk for infection (eg, unexplained jaundice, prolonged rupture of
membranes, maternal fever, etc); infection excluded by sterile cultures (CSF, blood, urine) and lack of clinical evidence of
bacterial or viral infection.
Δ CSF obtained in the emergency department during evaluation for possible infection; infection was excluded by sterile
cultures (CSF, blood, urine, and negative polymerase chain reaction for enterovirus).
◊ Only two infants had CSF WBC >30/mm 3: one <7 days of age with 130 WBC/mm 3 and one 15 to 21 days of age with 62
WBC/mm 3.
§ Includes 29 preterm infants and 1 infant who was 2190 g at 40 weeks' gestation.
¥ Includes all infants with birth weight <2500 g.

References:
1. Naidoo BT. The cerebrospinal fluid in the healthy newborn infant. S Afr Med J 1968; 42:933.
2. Sarff LD, Lynn H, Platt MD, et al. Cerebrospinal fluid evaluation in neonates: Comparison of high risk infants with and
without meningitis. J Pediatr 1976; 88:473.
3. Pappu L. CSF cytology in the neonate. Am J Dis Child 1982; 136:297.
4. Ahmed A. Cerebrospinal fluid values in the term neonate. Pediatr Infect Dis J 1996; 15:298.
5. Chadwick SL, Wilson JW, Levin JE, Martin JM. Cerebrospinal fluid characteristics of infants who present to the
emergency department with fever: Establishing normal values by week of age. Pediatr Infect Dis J 2011; 30:e63.
6. Byington CL, Kendrick J, Sheng X. Normative cerebrospinal fluid profiles in febrile infants. J Pediatr 2011; 158:130.
7. Rodriguez AF, Kaplan SL, Mason EO. Cerebrospinal fluid values in the very low birth weight infant. J Pediatr 1990;
116:971.

Graphic 54464 Version 15.0

Suggested antimicrobial regimens in the management of neonatal sepsis in term
and late preterm infants

Antibiotic regimen

Empiric therapy

Early onset (<7 days) Ampicillin AND gentamicin

Late onset (≥7 days): Admitted from the community Ampicillin AND gentamicin

Late onset (≥7 days): Hospitalized since birth Gentamicin AND vancomycin

Special circumstances:

Suspected meningitis - early onset Ampicillin AND gentamicin*

Suspected meningitis - late onset, admitted from the Ampicillin, gentamicin, AND cefotaxime ¶
community

Suspected meningitis - late onset, hospitalized since Gentamicin, vancomycin, AND cefotaxime ¶
birth

Suspected pneumonia Ampicillin AND gentamicin

Alternatives:
Ampicillin AND cefotaxime ¶, OR
Vancomycin AND cefotaxime ¶, OR
Vancomycin AND gentamicin

Suspected infection of soft tissues, skin, joints, or Vancomycin or vancomycin AND nafcillin
bones (S. aureus is a likely pathogen)

Suspected intravascular catheter-related infection Vancomycin AND gentamicin

Suspected infection due to organisms found in the Ampicillin, gentamicin, AND clindamycin
gastrointestinal tract (eg, anaerobic bacteria) Alternatives:
Ampicillin, gentamicin, AND metronidazole OR
Piperacillin-tazobactam AND gentamicin

Pathogen-specific therapy

Group B Streptococcus Penicillin G

Escherichia coli: Ampicillin-sensitive Ampicillin

Escherichia coli: Ampicillin-resistant Cefotaxime ¶

Alternative:
Meropenem

Multidrug-resistant gram-negative bacilli (including Meropenem

ESBL-producing organisms)

Listeria monocytogenes Ampicillin AND gentamicin

Methicillin-susceptible S. aureus (MSSA) Nafcillin OR cefazolin

Methicillin-resistant S. aureus (MRSA) Vancomycin

Coagulase-negative staphylococci Vancomycin

ESBL: extended-spectrum beta-lactamase.

* Cefotaxime should be added to the empiric regimen for suspected early-onset meningitis if the CSF Gram stain reveals
gram-negative bacilli.
¶ If cefotaxime is not available, alternative agents include ceftazidime, ceftriaxone (not to be used in infants with clinically
significant hyperbilirubinemia or those receiving concurrent IV calcium [including parenteral nutrition]), or meropenem.
Meropenem is preferred if there is concern for infection due to a multidrug-resistant gram-negative organism.

References:
 1. Edwards MS, Baker CJ. Bacterial infections in the neonate. In: Principles and Practice of Pediatric Infectious Diseases,
4th ed, Long SS, Pickering LK, Prober CG (Eds), Elsevier Saunders, Philadelphia 2012. p.538.
2. Nizet V, Klein JO. Bacterial sepsis and meningitis. In: Infectious diseases of the Fetus and Newborn Infant, 7th ed,
Remington JS, et al (Eds), Elsevier Saunders, Philadelphia 2010. p.222.
3. American Academy of Pediatrics. Group B streptococcal infections. In: Red Book: 2015 Report of the Committee on
Infectious Diseases, 30th ed, Kimberlin DW (Ed), American Academy of Pediatrics, 2015. p.745.
4. American Academy of Pediatrics. Escherichia coli and other Gram-negative bacilli (septicemia and meningitis in
neonates). In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW (Ed), American
Academy of Pediatrics, Elk Grove Village, IL 2015. p.340.

Graphic 102574 Version 5.0

Common bacterial agents causing neonatal sepsis in term infants

Frequency of isolation
Bacterial species
Early-onset Late-onset

Group B Streptococcus +++ +++

Escherichia coli +++ ++

Klebsiella spp. + +

Enterobacter spp. + +

Listeria monocytogenes + +

Other enteric gram-negatives + +

Non-enteric gram-negatives* + +

Viridans streptococci + +

Staphylococcus aureus + +++

Citrobacter spp. 0 +

Salmonella spp. 0 +

Coagulase-negative staphylococci 0 +

Enterococcus spp. 0 +

+++: commonly associated; ++: frequently associated; +: occasionally associated; 0: rarely associated.

* Includes nontypable Hemophilus influenzae and Neisseria meningitidis.

Adapted from: Edwards MS, Baker CJ. Bacterial infections in the neonate. In: Principles and Practice of Pediatric Infectious
Disease, 4th ed, Long SS, Pickering LK, Prober CG. Elsevier Saunders, Philadelphia 2012.

Graphic 61061 Version 6.0

Antimicrobial therapy for group B streptococcal infections in neonates and young
infants

Site(s) of infection Empiric therapy* Definitive therapy ¶ Duration of therapy

Early-onset (from birth through day 6)

Bacteremia/sepsis/pneumonia Ampicillin 150 mg/kg every Penicillin G: 50,000 to 10 days
12 hours 100,000 units/kg per day
PLUS divided every 12 hours

Gentamicin 4 mg/kg every

24 hours for infants born
at ≥35 weeks gestation; 3
mg/kg every 24 hours for
infants born at <35 weeks
gestation

Meningitis Ampicillin 100 to 150 Penicillin G: 250,000 to 14 to 21 days Δ

mg/kg every 8 hours 450,000 units/kg per day
PLUS divided every 8 hours

Gentamicin 4 mg/kg every

24 hours for infants born
at ≥35 weeks gestation; 3
mg/kg every 24 hours for
infants born at <35 weeks
gestation

Late-onset (beyond day 6 after birth)

Bacteremia without a focus Ampicillin, nafcillin, or Penicillin G 10 days

vancomycin 75,000 to 150,000 units/kg
PLUS per day divided every 8
Gentamicin or cefotaxime ◊ hours

Meningitis Ampicillin and/or Penicillin G 14 to 21 days Δ

vancomycin 450,000 to 500,000
PLUS units/kg per day divided
Gentamicin or cefotaxime ◊ every 6 hours

Cellulitis/adenitis Nafcillin or vancomycin Penicillin G 10 to 14 days

PLUS 75,000 to 150,000 units/kg
Gentamicin or cefotaxime ◊ per day divided every 8
hours

Septic arthritis Nafcillin or vancomycin Penicillin G 14 to 21 days

PLUS 75,000 to 150,000 units/kg
Cefotaxime ◊ per day divided every 8
hours

Osteomyelitis Nafcillin or vancomycin Penicillin G 21 to 28 days

PLUS 75,000 to 150,000 units/kg
Cefotaxime ◊ per day divided every 8
hours

Urinary tract infection Ampicillin, nafcillin, or Penicillin G 10 days

vancomycin 75,000 to 150,000 units/kg
PLUS per day divided every 8
Gentamicin or cefotaxime ◊ hours
The antibiotic doses listed above are for use in neonates and young infants weighing ≥1 kg with normal renal function.
For additional dosing detail, refer to the Lexicomp pediatric and neonatal drug information monographs included within
UpToDate.

GBS: group B streptococcus; CSF: cerebrospinal fluid; IV: intravenous.

* Selection will depend on age and presumed source of infection (maternal, hospital, or community). Local susceptibility
patterns should also be considered.
¶ Transition from empiric to definitive therapy should occur once GBS is identified by culture; clinical improvement is evident;
and for meningitis, CSF is sterile at 24 to 48 hours of therapy.
Δ Fourteen days is sufficient for uncomplicated cases of GBS meningitis.
◊ If cefotaxime is not available, alternative agents include ceftazidime or ceftriaxone. Ceftriaxone should not to be used in
infants with clinically significant hyperbilirubinemia or those receiving concurrent IV calcium (including parenteral nutrition).

References:
1. American Academy of Pediatrics. Group B streptococcal infections. In: Red Book: 2015 Report of the Committee on
Infectious Diseases, 30 th ed, Kimberlin DW (Ed), American Academy of Pediatrics, 2015. p.745.
2. American Academy of Pediatrics. Tables of antibacterial drug dosages, Table 4.2. In: Red Book: 2015 Report of the
Committee on Infectious Diseases, 30 th ed, Kimberlin DW (Ed), American Academy of Pediatrics, Elk Grove Village, IL
2015. p.882.
3. Medications. In: Guidelines for Acute Care of the Neonate, 22nd Ed, Adams JM, Fernandes CJ (Eds), Baylor College of
Medicine, Houston, TX 2014. p.89.
4. Rao SC, Srinivasjois R, Hagen R, et al. One dose per day compared to multiple doses per day of gentamicin for
treatment of suspected or proven sepsis in neonates. Cochrane Database Syst Rev 2011 Nov 9(11).

Graphic 66906 Version 9.0

Contributor Disclosures
Morven S Edwards, MD Grant/Research/Clinical Trial Support: Pfizer [Group B Streptococcus]. Leonard E
Weisman, MD Grant/Research/Clinical Trial Support: Vax-Immune [Ureaplasma diagnosis, vaccines, antibodies,
other medical diagnostics and pre-analytical devices]. Consultant/Advisory Boards: Glaxo-Smith Kline [Malaria
vaccine]; NIAID [Staphylococcus aureus (Mupirocin)]. Patent Holder: Baylor College of Medicine [Ureaplasma
diagnosis, vaccines, antibodies, process for preparing biological samples]. Equity Ownership/Stock Options: Vax-
Immune [Ureaplasma diagnosis, vaccines, antibodies, other medical diagnostics and pre-analytical
devices]. Sheldon L Kaplan, MD Grant/Research/Clinical Trial Support: Pfizer [Streptococcus pneumonia
(PCV13, linezolid)]; Merck [Staphylococcus aureus (Tedizolid)]; Allergen [Osteomyelitis (Ceftaroline)].
Consultant/Advisory Boards: Pfizer [Staphylococcus aureus (vaccine development); linezolid]. Other Financial
Interest: Pfizer [Speaker on PCV13, linezolid]; Medscapre [Video discussion on bacterial meningitis]; Elsevier
[Co-editor (Feigin and Cherry Textbook of Pediatric Infectious Diseases)]. Carrie Armsby, MD, MPH Nothing to
disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting 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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