Define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates.
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.
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.
For EOS in preterm infants, two ampicillin doses (50 mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity.
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Erin Campbell, MS provided editorial review and submission of this manuscript. Ms. Campbell did not receive compensation for her contributions, apart from her employment at the institution where this study was conducted. This work was funded under the National Institute of Child Health and Human Development (NICHD) contract (HHSN275201000003I) for the Pediatric Trials Network (PI Danny Benjamin). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The authors declare no competing interests.
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Le, J., Greenberg, R.G., Yoo, Y. et al. Ampicillin dosing in premature infants for early-onset sepsis: exposure-driven efficacy, safety, and stewardship. J Perinatol 42, 959–964 (2022). https://doi.org/10.1038/s41372-022-01344-2