American Academy of Pediatrics Treatment for Early-Onset Neonatal Sepsis
The AAP recommends ampicillin plus gentamicin as first-line empiric therapy for suspected or proven early-onset neonatal sepsis (first 72 hours of life), with cefotaxime as a reasonable alternative to gentamicin when gram-negative meningitis is suspected. 1
Standard First-Line Regimen
Ampicillin plus gentamicin provides optimal coverage against the most common early-onset pathogens: Group B Streptococcus, E. coli, Listeria monocytogenes, and other Enterobacteriaceae 1, 2
Ampicillin dosing for neonates ≤28 days:
Gentamicin dosing must be adjusted based on gestational and postnatal age, typically 4 mg/kg IV every 24 hours for most neonates 4, 5
Alternative Regimen
Third-generation cephalosporins (cefotaxime) represent a reasonable alternative to aminoglycosides, particularly when gram-negative meningitis is suspected or confirmed 1
However, ampicillin/cefotaxime carries increased mortality risk compared to ampicillin/gentamicin (adjusted OR 1.5,95% CI 1.4-1.7) and should be reserved for specific indications rather than routine empiric use 6
Special Population: Preterm Infants <35 Weeks
All preterm infants born <35 weeks' gestation with high-risk delivery characteristics (cervical insufficiency, preterm labor, PROM, chorioamnionitis, nonreassuring fetal status) should receive empiric antibiotics even after adequate intrapartum prophylaxis 1, 7
Blood culture and antibiotic treatment are mandatory for these high-risk preterm deliveries 1
Lumbar puncture with CSF analysis should be performed if the infant is stable and early-onset GBS disease is highly suspected 1
Special Population: Term and Late Preterm Infants ≥35 Weeks
Three risk assessment strategies are acceptable per AAP guidelines: categorical risk assessment, multivariate risk assessment (sepsis calculator), or clinical condition-based assessment 1
The Neonatal Early-Onset Sepsis Calculator (Kaiser Permanente) can reduce unnecessary antibiotic exposure when applied appropriately, using a baseline EOS risk of 0.5 per 1,000 live births in the United States 1, 8
All infants with clinical signs of sepsis or maternal fever ≥100.4°F require empiric antibiotics regardless of risk assessment method 1
Critical Timing and Duration
Obtain blood cultures before initiating antibiotics, but never delay treatment waiting for results 9, 10
Discontinue antibiotics at 48 hours if cultures are negative and clinical probability of sepsis is low, to avoid prolonged unnecessary exposure 4, 2
Prolonged empiric antibiotic therapy (≥5 days) in preterm infants is associated with increased risks of late-onset sepsis, necrotizing enterocolitis, and mortality 2, 7
Treatment duration for culture-confirmed sepsis is typically 10-14 days for bacteremia without focal infection 4, 11
Specific Clinical Scenarios Requiring Broad-Spectrum Coverage
All asymptomatic infants born to mothers with suspected chorioamnionitis should receive broad-spectrum antibiotics 1
**All premature infants (<37 weeks) require broad-spectrum antibiotics** if any of the following: chorioamnionitis, PROM >18 hours, or inadequate GBS intrapartum prophylaxis 1
Common Pitfalls to Avoid
Never use ceftriaxone in neonates due to risk of bilirubin displacement and kernicterus; cefotaxime is the appropriate third-generation cephalosporin if needed 9, 4
Avoid routine use of third-generation cephalosporins as first-line therapy, as this promotes rapid emergence of resistant organisms and has demonstrated antagonistic interactions with penicillins 11, 6
Do not continue antibiotics beyond 48 hours in well-appearing infants with negative cultures and low clinical suspicion, as this increases subsequent morbidity and mortality 2, 7
Failing to obtain CSF when meningitis is suspected results in inadequate dosing and duration, as meningitis requires higher ampicillin doses (150-200 mg/kg/day) and longer treatment courses 4, 3