氨苄西林治疗早产儿早发性败血症的剂量：基于暴露的疗效、安全性和管理。
Ampicillin dosing in premature infants for early-onset sepsis: exposure-driven efficacy, safety, and stewardship.
机构信息
Skaggs School of Pharmacy and Pharmaceutical Science, University of California, San Diego, La Jolla, CA, USA.
Department of Pediatrics, Duke University, Durham, NC, USA.
出版信息
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 (C ≤ 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 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.
CONCLUSIONS
For EOS in preterm infants, two ampicillin doses (50 mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity.
目的
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。
研究设计
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。
结果
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。
结论
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。
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