Skaggs School of Pharmacy and Pharmaceutical Science, University of California, San Diego, La Jolla, CA, USA.
Department of Pediatrics, Duke University, Durham, NC, USA.
J Perinatol. 2022 Jul;42(7):959-964. doi: 10.1038/s41372-022-01344-2. Epub 2022 Feb 24.
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 (C ≤ 140 mcg/mL), and duration limited to 48 h.
Among 34,689 newborns, all dosing regimens provided concentrations above MIC through 48 h, but C 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.
为早产儿早发性败血症（EOS）经验性治疗定义最佳氨苄西林剂量。
我们模拟了新生儿（出生体重<1500 克；胎龄 22-27 周）的氨苄西林浓度，总结了三种 48 小时方案：高剂量 100mg/kg Q8hr、中剂量 100mg/kg Q12hr 和标准剂量 50mg/kg Q12hr。分析了浓度高于最低抑菌浓度（MIC）、低于神经毒性阈值（C≤140 mcg/mL）和持续时间限于 48 小时的浓度数据。
在 34689 名新生儿中，所有剂量方案在 48 小时内均提供了高于 MIC 的浓度，但 C 超过了神经毒性阈值。采用 4 剂标准方案，超过 90%的新生儿在 48 小时后维持浓度> MIC。采用 2 剂方案，新生儿在 48 小时的培养窗内维持平均浓度> MIC 且低于神经毒性水平。22-24 周胎龄的婴儿比 25-27 周胎龄的婴儿具有更高的药物浓度和更长的暴露时间。
对于早产儿 EOS，两次氨苄西林剂量（50mg/kg）可提供最佳杀菌暴露，同时最大限度地降低潜在毒性。
