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Offi cial reprint from UpToDatewww.uptodate.com ©2015 UpToDate

Author Morven S Edwards, MD

Section EditorsLeonard E Weisman, MDSheldon L Kaplan, MD

Deputy Editor Carrie Armsby, MD, MPH

Management and outcome of sepsis in term and late preterm infants

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Aug 2015. | This topic last updated: Jul 13, 2015.

INTRODUCTION — Sepsis is an important cause of morbidity and mortality among newborn infants. Although the

incidence of sepsis in term and late preter m 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 Center for Disease Control (CDC) [1,2].

The treatment and outcome of sepsis in term and late preterm infants will be reviewed here. T he 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 infection, and the evaluation of

febrile or ill-appearing newborns are discussed separately:

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

Neonatal sepsis is classified accor ding to the infant's age at the onset of symptoms:

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:

®

®

(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" .)

(See "Treatment and prevention of bacterial sepsis in the preterm infant".)

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

(See "Evaluation and management of fever in the neonate and young infant (younger than three months of

age)", section on 'Neonates (0 to 28 days)'.)

(See "Approach to the septic-appearing infant".)

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 blood stream [ 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 between 34 and 36 completed weeks of

gestation [5]. (See "Late preterm infants".)

Preterm infants are those born at less than 34 weeks of gestation [5].

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].

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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, and evaluation 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 suggestingmeningitis 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'):

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

Maintaining adequate oxygenation and perfusion (see "Oxygen monitoring and therapy 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")

Ill-appearance (see "Approach to the septic-appearing infant")

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')

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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 (E. 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 S. aureus bacteremia that was not susceptible to ampicillin and gentamicin, there were nocomplications 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 addition of a third-generation cephalosporin to the regimen of ampicillin and gentamicin is warranted for infantswith 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 cefotaxime 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 intravenously every six hours; the dosing of gentamicin

is 4 mg/kg per dose intravenously 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

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 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]. (See "Clinical manifestations of unconjugated

hyperbilirubinemia in term and late preterm infants", section on 'Neurologic manifestations'.)

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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 infants >7 days

of life, the dosing of vancomycin is dependent on postmenstrual age (PMA) [8]:

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

Culture-proven sepsis — In neonates with culture-proven sepsis, the usual course of therapy is 10 days

[1,3,13,17,18]. 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 — Guidelines for the treatment of the most common causative organisms of

neonatal sepsis are (table 3):

Group B streptococcus — The drug of choice for 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 5A-B). (See "Group

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

Escherichia coli — In patients with Escherichia coli (E. coli ) sepsis sensitive to ampicillin 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 is often employed if the isolate is susceptible.

Other gram-negative bacilli — Nonmeningeal infections caused by E. coli , Klebsiella, Proteus,

Salmonella, or Shigella should be treated with a single agent, based upon the antimicrobial susceptibility profile.

30 to 37 weeks PMA – 15 mg/kg per dose every 12 hours

>37 weeks PMA – 15 mg/kg per dose every 8 hours

Suspected meningitis – When lumbar puncture suggests meningitis, cefotaxime should be included in the

regimen to provide an extended spectrum for enteric gram-negative rods and for optimal activity in the CSF

against pneumococci. Treatment of bacterial meningitis in neonates is discussed in detail separately. (See

"Bacterial meningitis in the neonate: Treatment and outcome", section on 'Empirical therapy'.)

Suspected pneumonia − Empiric regimens for treatment of infants with a pulmonary focus of infection include

ampicillin and gentamicin, ampicillin and cefotaxime, vancomycin and cefotaxime, or vancomycin and

gentamicin. Treatment of pneumonia in neonates is discussed in detail separately. (See "Neonatal

pneumonia", section on 'Treatment'.)

If there is a focus of infection involving the soft tissues, skin, joints, or bones (in which case S. aureus is a

likely pathogen), vancomycin should be substituted for ampicillin [16]. In a toxic-appearing infant, nafcillin

should also be added.

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.

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.

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Antimicrobial treatment for infections caused by Enterobacter , Serratia, or Pseudomonas should be selected based

upon the susceptibility profile of the organism.

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:

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:

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 [1,19].

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

S. 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.

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

If lumbar puncture has not been performed, ampicillin should be continued at a meningitic dose.

Management of infants with cerebrospinal fluid (CSF) pleocytosis and/or positive CSF culture is discussed

separately. (See "Bacterial meningitis in the neonate: Treatment and outcome" .)

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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 [17,18,20]:

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 effectivematernal 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 [12,28]. 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 [29]. (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 [9,28,30].

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 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 writtenat the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable

with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these

topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on

"patient info" and the keyword(s) of interest.)

SUMMARY AND RECOMMENDATIONS

Intravenous immunoglobulin (IVIG) infusions [21,22]

Granulocyte transfusions [23]

Granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) [ 24,25]

Pentoxifylline [26]

Lactoferrin [27]

th th

th th

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

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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 septic-appearing infant")•

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).

The empiric regimen for early-onset sepsis without an apparent focus consists of ampicillin and

gentamicin. (See 'Early-onset sepsis' above.)

•

Empiric antibiotic regimens for late-onset sepsis without an apparent focus are as follows (see 'Late-

onset sepsis' above):

•

For neonates admitted from the community, we suggest ampicillin and gentamicin.-

For infants who continue to be hospitalized from birth, we suggest vancomycin and gentamicin.-

Empiric antibiotic regimens for suspected neonatal sepsis (early- or late-onset) with certain special

circumstances are as follows (see 'Special circumstances' above):

•

If there is concern of meningitis, we suggest adding cefotaxime to the regimen. (See "Bacterial

meningitis in the neonate: Treatment and outcome", section on 'Empirical therapy' .)

-

If there is concern for pneumonia, we suggest a regimen of ampicillin and cefotaxime or

vancomycin and cefotaxime.

-

If there is a focus of infection involving the soft tissues, skin, joints, or bones (in which case S.

aureus is a likely pathogen), we suggest substituting vancomycin or, in toxic-appearing infants,

vancomycin plus nafcillin for ampicillin.

-

If intravascular catheter-related infection is a concern, we suggest vancomycin and gentamicin.-

If an intestinal source for sepsis is suspected, we suggest adding clindamycin, or other suitable

antibiotic such as metronidazole.

-

Antibiotic therapy is altered based upon isolation of the causative agent and its antimicrobial susceptibility

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REFERENCES

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2. Verani JR, McGee L, Schrag SJ, Division of Bacterial Diseases, National Center for Immunization andRespiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group Bstreptococcal disease--revised guidelines from CDC, 2010. MMWR Recomm Rep 2010; 59:1.

3. Edwards, MS, Baker, CJ. Sepsis in the Newborn. In: Krugman's Infectious Diseases of Children, 11th ed,

Gershon, AA, Hotez, PJ, Katz, SL (Eds), Mosby, Philadelphia 2004, p. 545.4. Wynn JL, Wong HR, Shanley TP, et al. Time for a neonatal-specific consensus definition for sepsis. Pediatr

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6. American Academy of Pediatrics. Group B streptococcal infections. In: Red Book: 2015 Report of theCommittee on Infectious Diseases, 30th ed, Kimberlin DW (Ed), American Academy of Pediatrics, 2015.p.745.

7. Rao SC, Ahmed M, Hagan R. 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 2006; :CD005091.

8. 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.

9. Stoll BJ, Hansen NI, Sánchez PJ, et al. Early onset neonatal sepsis: the burden of group B Streptococcaland E. coli disease continues. Pediatrics 2011; 127:817.

10. Muller-Pebody B, Johnson AP, Heath PT, et al. Empirical treatment of neonatal sepsis: are the currentguidelines adequate? Arch Dis Child Fetal Neonatal Ed 2011; 96:F4.

11. Maayan-Metzger A, Barzilai A, Keller N, Kuint J. Are the "good old" antibiotics still appropriate for early-onset neonatal sepsis? A 10 year survey. Isr Med Assoc J 2009; 11:138.

12. Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Empiric use of ampicillin and cefotaxime, compared withampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonataldeath. Pediatrics 2006; 117:67.

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 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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13. American Academy of Pediatrics. Escherichia coli and other Gram-negative bacilli (septicemia andmeningitis 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.

14. Gulian JM, Dalmasso C, Gonard V. Interaction of beta-lactam antibiotics on bilirubin-albumin complex:comparison by three methods, total bilirubin, unbound bilirubin and erythrocyte-bound bilirubin.Chemotherapy 1990; 36:91.

15. Martin E, Fanconi S, Kälin P, et al. Ceftriaxone--bilirubin-albumin interactions in the neonate: an in vivostudy. Eur J Pediatr 1993; 152:530.

16. Fortunov RM, Hulten KG, Hammerman WA, et al. Community-acquired Staphylococcus aureus infections interm and near-term previously healthy neonates. Pediatrics 2006; 118:874.

17. Nizet V, Klein JO. Bacterial sepsis and meningitis. In: Infectious diseases of the Fetus and Newborn Infant,7th ed, Remington JS, et al (Eds), WB Saunders, Philadelphia 2010. p.222.

18. Gerdes JS. Diagnosis and management of bacterial infections in the neonate. Pediatr Clin North Am 2004;51:939.

19. Polin RA, Watterberg K, Benitz W, Eichenwald E. The conundrum of early-onset sepsis. Pediatrics 2014;133:1122.

20. Cohen-Wolkowiez M, Benjamin DK Jr, Capparelli E. Immunotherapy in neonatal sepsis: advances intreatment and prophylaxis. Curr Opin Pediatr 2009; 21:177.

21. INIS Collaborative Group, Brocklehurst P, Farrell B, et al. Treatment of neonatal sepsis with intravenous

immune globulin. N Engl J Med 2011; 365:1201.22. Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or proven infection in neonates. Cochrane

Database Syst Rev 2015; 3:CD001239.

23. Pammi M, Brocklehurst P. Granulocyte transfusions for neonates with confirmed or suspected sepsis andneutropenia. Cochrane Database Syst Rev 2011; :CD003956.

24. 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.

25. Carr R, Modi N, Doré C. G-CSF and GM-CSF for treating or preventing neonatal infections. CochraneDatabase Syst Rev 2003; :CD003066.

26. Pammi M, Haque KN. Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates.

Cochrane Database Syst Rev 2015; 3:CD004205.

27. Pammi M, Abrams SA. Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates.Cochrane Database Syst Rev 2011; :CD007138.

28. Weston EJ, Pondo T, Lewis MM, et al. The burden of invasive early-onset neonatal sepsis in the UnitedStates, 2005-2008. Pediatr Infect Dis J 2011; 30:937.

29. Payne NR, Burke BA, Day DL. Correlation of clinical and pathologic findings in early onset neonatal group Bstreptococcal infection with disease severity and prediction of outcome. Pediatr Infect Dis 1998; 7:836.

30. Escobar GJ, Li DK, Armstrong MA, et al. Neonatal sepsis workups in infants >/=2000 grams at birth: Apopulation-based study. Pediatrics 2000; 106:256.

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GRAPHICS

Differential diagnosis of neonatal sepsis

Diagnosis Distinguishing

features Diagnostic tests

Other systemic neonatal infections

Viral infections:

Herpes simplex virus Mucocutaneous vesicles, CSF

pleocytosis, elevated CSF

protein, thrombocytopenia,

hepatitis

Viral culture; HSV PCR

Enteroviruses Fulminant systemic disease,

myocarditis, hepatitis,

encephalitis

Viral culture; EV PCR

Parechovirus Encephalitis/meningitis, rash

on palms and soles

HPeV PCR (available through

CDC)

Cytomegalovirus Thrombocytopenia,

periventricular intracranial

calcifications, microcephaly,

sensorineural hearing loss,

chorioretinitis

Viral culture; CMV PCR

Influenza viruses Respiratory symptoms,

rhinorrhea, gastrointestinal

symptoms

Viral culture; influenza-specific

antigen detection or

immunofluorescence assay

Respiratory syncytial

virus

Respiratory symptoms,

rhinorrhea, cough, apnea,

pneumonia

Viral culture; RSV-specific

antigen detection or

immunofluorescence assay

Spirochetal infections –

Syphilis

Skeletal abnormalities

(osteochondritis and

periostitis), pseudoparalysis,

persistent rhinitis,

maculopapular rash

(particularly on palms and soles

or in diaper area)

RPR or VDRL

Parasitic infections:Congenital malaria Anemia, splenomegaly,

jaundice

Detection of parasitemia on

blood smear

Toxoplasmosis Intracranial calcifications

(diffuse), hydrocephalus,

chorioretinitis, mononuclear

CSF pleocytosis, elevated CSF

protein

T. gondii serology

Fungal infection –

Candidiasis

Persistent hyperglycemia,

thrombocytopenia, multiorgan

Isolation of Candida in blood,

urine or CSF culture

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failure

Non-infectious 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;

sweating, sneezing, nasal

stuffiness, and yawning

Positive drug screening tests

CNS insult (eg, anoxia or

hemorrhage)

History of perinatal asphyxia;

focal neurologic findings or

seizures

Abnormal neuroimaging

studies

Hypothyroidism Hypoton ia, leth argy,

hypothermia, large fontanels

Abnormal T4 or TSH level on

newborn screen

Congenital adrenal

hyperplasia

Ambiguous genitalia (females),

adrenal insufficiency and salt-wasting (hyponatremia,

hyperkalemia, dehydration)

Abnormal 17a-

hydroxyprogesterone level onnewborn screen

Non-infectious causes of respiratory and cardiocirculatory symptoms in neonates

Transient tachypnea of the

newborn

Onset of symptoms within two

hours after delivery; symptoms

usually resolve within 24 hours

CXR findings include increased

lung volumes, mild

cardiomegaly, prominent

vascular markings, fluid in the

interlobar fissures, and pleural

effusions

Respiratory distress

syndrome

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

CXR findings include low lung

volume and diffuse

reticulogranular ground glass

appearance with air

bronchograms

Meconium aspiration History of meconium-stained

amniotic fluid; respiratory

distress occurs immediately

after birth

Initial CXR may show streaky,

linear densities; as the disease

progresses, the lungs may

appear hyperinflated with

diffuse patchy densities

Pneumothorax Asymmetric chest rise,

decreased breath sounds on

affected side; hypotension (in

cases of tension

pneumothorax)

CXR will usually detect

symptomatic pneumothoraces

Congenital anomalies

(including tracheal-

esophageal fistula, choanal

atresia, and diaphragmatic

Often occur with other

congenital anomalies including

VACTERL and CHARGE

associations; choanal atresia is

CDH is often diagnosed by

routine antenatal ultrasound

screening; postnatal CXR

shows herniation of abdominal

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hernia) characterized by noisy labored

breathing while feeding

contents into hemithorax; TEF

is diagnosed with upper

gastrointestinal series and/or

bronchoscopy

Neonatal abstinence

syndrome

History of maternal drug use;

sweating, sneezing, nasal

stuffiness, and yawning

Positive drug screening tests

Cardiac arrhythmias (eg,

supraventricular

tachycardia)

Abrupt onset and termination

of rapid heart rate

Abnormal ECG

Congenital heart disease 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

Abnormal hyperoxia test;

abnormal echocardiography

Non-infectious causes of neurologic symptoms in neonates

Hypoglycemia Common in infants who are

large for gestational age and/or

infants of diabetic mothers

Abnormal blood glucose level

Hypercalcemia Increased n euromuscular

irritability and seizures;

associated with prematurity,

maternal diabetes, and

perinatal asphyxia

Abnormal serum calcium level

Hypermagnesemia Generalized hypotonia,

respiratory depression and

apnea; typically results from

maternal treatment with

magnesium sulfate

Abnormal serum magnesium

level

CNS insult (eg, anoxia or

hemorrhage)

History of perinatal asphyxia;

focal neurologic findings or

seizures

Abnormal neuroimaging

studies

Congenital CNS

malformations (eg,

hydrocephalus)

Abnormal head circumference Abnormal neuroimaging

studies

Neonatal abstinence

syndrome

History of maternal drug use;

sweating, sneezing, nasal

stuffiness, and yawning

Positive drug screening tests

Inborn errors of metabolism Otherwise unexplained acid-

base disorders,

hyperammonemia,

hypoglycemia, hematologic

abnormalities, liver

dysfunction, and renal disease

Positive newborn screen for

inborn errors of metabolism

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Pyridoxine deficiency Refractory seizures Abnormal plasma pyridoxal-5-

phophate level

HSV: herpes simplex virus; PCR: polymerase chain reaction; CSF: cerebral spinal fluid; HPeV: human

parechovirus; EV: enterovirus; 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; TEF: tracheoesophageal fistula; 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; 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, 7th ed, Remington JS, et al (Eds), Elsevier Saunders, Philadelphia 2010.

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Characteristics of cerebrospinal fluid in term and preterm neonates

without bacterial meningitis

Age

Mean

WBC/mm

(range or

90thpercentile)

ANC/mm

or percent

PMNs

(range)

Mean

protein

(mg/dL)

(range or±SD)

Mean

glucose

(mg/dL)

(range or±SD)

Term neonates evaluated in the nursery setting

0 to 24 hours

(n = 135)*

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

0 to 10 days

(n = 87)

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

0 to 32 days

(n = 24)

11 (1 to 38) 21 percen t (0 t o

100)

NR NR

Term neonates evaluated in the emergency department setting

0 to 7 days

(n = 17)

15.3 (1 to 130) 4.4/mm (0 to

65)

80.8 (±30.8) 45.9 (±7.5)

0 to 7 days

(n = 118)

8.6 (90

percentile: 26)

NR 106.4 (90

percentile: 153)

NR

1 to 28 days

(n = 297)

6.1 (0 to 18) NR 75.4 (15.8 to

131)

45.3 (30 to 61)

0 to 30 days

(n = 108)

7.3 (0 to 130) 0.8/mm (0 to

65)

64.2 (±24.2) 51.2 (±12.9)

8 to 14 days

(n = 101)

3.9 (90

percentile: 9)

NR 77.6 (90

percentile: 103)

NR

8 to 14 days

(n = 33)

5 .4 (0 to 18) 0 .1/mm (0 to

1)

69 (±22.6) 54.3 (±17)

15 to 22 days

(n = 107)

4.9 (90

percentile: 9)

NR 71 (90

percentile: 106)

NR

15 to 21 days

(n = 25)

7 .7 (0 to 62) 0 .2/mm (0 to

2)

59.8 (±23.4) 46.8 (±8.8)

22 to 28 days(n = 141)

4.5 (90percentile: 9)

NR 68.7 (90percentile: 85)

NR

22 to 30 days

(n = 33)

4 .8 (0 to 18) 0 .1/mm (0 to

1)

54.1 (±16.2) 54.1 (±16.2)

Preterm or low birth weight neonates

0 to 28 days

(n = 30 )

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

0 to 32 days

(n = 22 )

7 (0 to 28) 1 6 percen t (0 to

100)

NR NR

33

[1]

3

¶[2]

¶[3]

Δ

[4]

3

[5]

th th

[6]

[4]

◊ 3

[5]

th th

[4]

3

[5]

th th

[4]

3

[5]th th

[4]

3

§ ¶[2]

￥ ¶[3]

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Very low birth weight neonates

<1000 g

0 to 7 days

(n = 6)

3 (1 to 8) 11 percent (0 to

50)

162 (115 to 222) 70 (41 to 89)

8 to 28

days

(n = 17)

4 (0 to 14) 8 percent (0 to

66)

159 (95 to 370) 68 (33 to 217)

29 to 84

days

(n = 15)

4 (0 to 11) 2 percent (0 to

36)

137 (76 to 269) 49 (29 to 90)

1000 to 1500 g

0 to 7 days

(n = 8)

4 (1 to 10) 4 percent (0 to

28)

136 (85 to 176) 74 (50 to 96)

8 to 28

days

(n = 14)

7 (0 to 44) 1 0 percen t (0 to

60)

137 (54 to 227) 59 (39 to 109)

29 to 84

days

(n = 11)

8 (0 to 23) 1 1 percen t (0 to

48)

122 (45 to 187) 47 (31 to 76)

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 : one <7 days of age with 130 WBC/mm , and one 15 t o 21

days of age with 62 WBC/mm .

§ 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 n ewborn infant. S Afr Med J 1968; 42:933.

2. Sarff LD, Lynn H, Platt MD, et al. Cerebrospinal fluid evaluation in n eonates: 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 infant s 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.

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3 3

3

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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:

Su spected men in gitis Am picillin , gen tam icin , AND cefotaxime

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 bones (S. aureus is a likely

pathogen)

Vancomycin or vancomycin AND nafcillin

Suspected intravascular catheter-related

infection

Vancomycin AND gentamicin

Suspected infection due to organisms

found in the gastrointestinal tract (eg,

anaerobic bacteria)

Ampicillin, gentamicin, AND clindamycin

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 ESBL-producing organisms)

Meropenem

Listeria monocytogenes Ampicillin AND gentamicin

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

Methicillin-resistant S. aureus (MRSA) Vancomycin

Coagulase-negative staphylococci Vancomycin

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ESBL: extended-spectrum beta-lactamase.

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 menin gitis. In: Infectious diseases of the Fetu s 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.

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Common bacterial agents causing neonatal sepsis in term infants

Bacterial species

Frequency of

isolation

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: E dwards 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.

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Intravenous treatment of early-onset group B streptococcal

infections

Site(s) of infection Empirical therapy Definitive

therapy*

Duration

of

therapy

Bacteremia/sepsis/pneumonia Ampicillin 150 mg/kg every 12

hours

Penicillin G:

50,000 to

100,000

units/kg per day

divided every 12

hours

10 days

PLUS

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 mg/kg

every 8 hours

Penicillin G:

250,000 to450,000

units/kg per day

divided every 8

hours

14 to 21

days

PLUS

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

GBS: Group B streptococcus; CSF: cerebrospinal fluid.

* Definitive therapy should not be started until GBS is identified by culture; clinical improvement is

evident; and for meningitis, CSF is sterile at 24 to 48 hours of therapy.¶ 14 days is sufficient for uncomplicated cases of GBS meningitis.

References:

1. 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.

2. 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.

3. American Academy of Pediatrics. Tables of antibacterial drug dosages, Table 4.2. 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.882.4. 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 71720 Version 8.0

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Intravenous treatment of late-onset group B streptococcal infections

in neonates and young infants

Site(s) of

infection

Empirical

therapy*

Definitive

therapy

Duration of

therapy

Bacteremia without a

focus

Ampicillin, nafcillin, or

vancomycin

PLUS

Gentamicin or

cefotaxime

Penicillin G

75,000 to 150,000

units/kg per day

divided every 8 hours

10 days

Meningitis Ampicillin and/or

vancomycin

PLUS

Gentamicin or

cefotaxime

Penicillin G

450,000 to 500,000

units/kg per day

divided every 6 hours

14 to 21 days

Cellulitis/adenitis Nafcillin or vancomycin

PLUS

Gentamicin or

cefotaxime

Penicillin G

75,000 to 150,000

units/kg per day

divided every 8 hours

10 to 14 days

Septic arthritis Nafcillin or vancomycin

PLUS

Cefotaxime

Penicillin G

75,000 to 150,000

units/kg per day

divided every 8 hours

14 to 21 days

Osteomyelitis Nafcillin or vancomycin

PLUS

Cefotaxime

Penicillin G

75,000 to 150,000

units/kg per day

divided every 8 hours

21 to 28 days

Urinary tract infection Ampicillin, nafcillin, or

vancomycin

PLUS

Gentamicin or

cefotaxime

Penicillin G

75,000 to 150,000

units/kg per day

divided every 8 hours

10 days

The antibiotic doses listed above are for use in neonates and young infants age >1 week andbody weight ≥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.

* Selection will depend on age and presumed source of infection (maternal, hospital, or community).

¶ Definitive therapy should be started once GBS is identified by culture; clinical improvement is evident;

and for meningitis, CSF is sterile at 24 to 48 hours of therapy.

References:

1. American Academy of Pediatrics. Group B streptococcal infections. In: Red Book: 2015 Report of

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17/9/2015 M anagem ent and outcome of sepsis in ter m and l ate pr eter m i nfants

http://www.uptodate.com/contents/management-and-outcome-of-sepsis- in-term-and-late-preterm -i nfants?topicKey=PEDS%2F5046&elapsedTimeMs=0&so… 2

the Committee on Infectious Diseases, 30th 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, 30th ed, Kimberlin DW (Ed), American

Academy of Pediatrics, Elk Grove Village, IL 2015. p.882.

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17/9/2015 M anagem ent and outcome of sepsis in ter m and l ate pr eter m i nfants

Disclosures: Morven S Edwards, MD Grant/Research/Clinical Trial Support: Pfizer Inc. [Group BStreptococcus]. Consultant/Advisory Boards: Novartis Vaccines [Group B Streptococcus]. Leonard E

Weisman, MD 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/StockOptions: Vax-Immune [Ureaplasma diagnosis, vaccines and antibodies]. Sheldon L Kaplan, MD

Grant/Research/Clinical Trial Support: Pfizer [vaccine (PCV13)]; Forest Lab [antibiotic (Ceftaroline)];

Optimer [antibiotic (fidaxomicin)]. Consultant/Advisory Boards: Pfizer [vaccine (PCV13)]. 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 beprovided to support the content. Appropriately referenced content is required of all authors and must

conform to UpToDate standards of evidence.

Conflict of interest policy

Disclosures