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

J Perinatol. 2022 Jul;42(7):959-964. doi: 10.1038/s41372-022-01344-2. Epub 2022 Feb 24.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Ampicillin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases* / drug therapy
  • Infant, Very Low Birth Weight
  • Sepsis* / drug therapy


  • Anti-Bacterial Agents
  • Ampicillin