Ampicillin Dosing in Premature Infants for Early-onset Sepsis: Exposure-driven Efficacy, Safety, and Stewardship

OBJECTIVE: Define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates. STUDY DESIGN: We simulated ampicillin concentrations in newborns (birthweight<1500g; gestational age 22–27 weeks), summarizing three 48-hour regimens: high 100mg/kg Q8hr, medium 100mg/kg Q12hr, and standard 50mg/kg Q12hr. Concentration data were analyzed for concentration above minimum inhibitory concentration (MIC), below neurotoxicity threshold (C(max)≤140mcg/mL), and duration limited to 48 hours. RESULTS: Among 34,689 newborns, all dosing regimens provided concentrations above MIC through 48 hours, but C(max) exceeded the neurotoxicity threshold. With the 4-dose standard regimen, >90% maintained concentrations >MIC beyond 48 hours. With the 2-dose regimen, newborns maintained the mean concentration >MIC within the 48-hour culture window and below neurotoxicity level. Infants 22–24 weeks’ gestation had higher drug concentrations and more prolonged exposure duration than 25–27 weeks’ gestation. CONCLUSIONS: For EOS in preterm infants, two ampicillin doses (50mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity.