Journal of the American Academy of Physician Associates (JAAPA)Recognizing and Managing Neonatal Sepsis

🎓 Expert Commentary / Peer Perspective

Neonatal sepsis — defined as systemic infection in infants under 28 days — presents across a spectrum from subtle feeding changes to septic shock, complicating diagnosis in a population with immature immune systems. Early-onset (EOS, within 72 hours) and late-onset (LOS, after 72 hours) subtypes differ in pathogen profile, transmission route, and risk stratification approach.

Clinical Considerations

• GBS and E. coli account for 70%–85% of EOS cases; pathogen predominance reverses between term and preterm neonates, with E. coli leading in preterm infants
• Blood culture remains the diagnostic gold standard, detecting bacteremia in 90%–97% of cases with a single draw; culture-negative sepsis exceeds culture-proven sepsis by up to 16-fold in the US
• The Neonatal EOS Risk Calculator incorporates gestational age, maternal GBS status, rupture of membranes duration, and intrapartum antibiotics to stratify risk and reduce unnecessary antibiotic exposure
• CRP and procalcitonin lack sufficient standalone specificity; consistently normal serial values over 48 hours are associated with low EOS likelihood and can support antibiotic discontinuation decisions

Practice Applications

• Consider LP for CSF analysis in all neonates 21 days or younger with suspected sepsis per AAP 2021 guideline
• Recognize that empiric ampicillin/gentamicin remains first-line; avoid routine cephalosporin addition due to fungal infection and resistance risk
• Discontinue empiric antibiotics within 36–48 hours in clinically stable neonates with negative cultures and normal labs
• Monitor for antimicrobial resistance patterns when selecting targeted therapy; vancomycin alternatives such as nafcillin are increasingly used for gram-positive coverage given rising resistance