Ampicillin dosing in premature infants for early-onset sepsis: exposure-driven efficacy, safety, and stewardship.

Journal Article (Journal Article)

OBJECTIVE: Define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates. STUDY DESIGN: We simulated ampicillin concentrations in newborns (birthweight < 1500 g; gestational age 22-27 weeks), summarizing three 48 h regimens: high 100 mg/kg Q8hr, medium 100 mg/kg Q12hr, and standard 50 mg/kg Q12hr. Concentration data were analyzed for concentration above minimum inhibitory concentration (MIC), below neurotoxicity threshold (Cmax ≤ 140 mcg/mL), and duration limited to 48 h. RESULTS: Among 34,689 newborns, all dosing regimens provided concentrations above MIC through 48 h, but Cmax exceeded the neurotoxicity threshold. With the 4-dose standard regimen, >90% maintained concentrations >MIC beyond 48 h. With the 2-dose regimen, newborns maintained the mean concentration >MIC within the 48 h 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 (50 mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity.

Full Text

Duke Authors

Cited Authors

  • Le, J; Greenberg, RG; Yoo, Y; Clark, RH; Benjamin, DK; Zimmerman, KO; Cohen-Wolkowiez, M; Wade, KC; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee,

Published Date

  • July 2022

Published In

Volume / Issue

  • 42 / 7

Start / End Page

  • 959 - 964

PubMed ID

  • 35210541

Pubmed Central ID

  • PMC9262754

Electronic International Standard Serial Number (EISSN)

  • 1476-5543

Digital Object Identifier (DOI)

  • 10.1038/s41372-022-01344-2


  • eng

Conference Location

  • United States