达普托米辛剂量优化在儿科黄金葡萄球菌细菌症:一个药理动力学/药理动力学调查
Katie B Olney1,2, Joel I Howard3,4, David S Burgess2
1Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, KY, USA.
目前针对儿童的达普托米辛剂量不足以治疗黄金杆菌菌菌症. 需要更高的剂量来确保疗效,并尽量减少儿科患者的毒性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 儿童传染病 儿童传染病
- 抗微生物药物管理委员会
背景情况:
- 达普托米辛是格兰阳性感染的关键抗生素,包括MRSA.
- 达普托米辛的最佳儿科剂量仍未确定.
- 这项研究解决了对儿童以证据为基础的剂量需求.
研究的目的:
- 为了评估儿科患者当前包装标签剂量中的达普托米辛暴露量.
- 为了确定最佳的达普托米辛剂量方案,以确保S. aureus bacteremia的儿童的有效性和安全性.
- 用蒙特卡洛模拟来确定有效性 (PTA_E) 和毒性 (PTA_T) 的目标实现.
主要方法:
- 蒙特卡洛模拟被用来模拟六个儿科年龄队列的达普托米辛暴露.
- 达成有效性目标的概率 (PTA_E) 基于AUC:MIC比率≥666.6.
- 对毒性达到目标的概率 (PTA_T) 基于Cmin ≥24.3 mg/L.
主要成果:
- 包装标签上的剂量导致所有评估的儿科年龄组的PTA_E低于最佳.
- 观察到的疗效不足,PTA_E在26.3%至50.1%之间.
- 为了达到所需的疗效和安全目标,需要更高的达普托米辛剂量 (10-24 mg/kg).
结论:
- 目前的达普托米辛包装标签剂量对于儿科S. aureus bacteremia是不够的.
- 建议的每日剂量为儿童≤6岁至少20毫克/千克,17毫克/千克儿童7-11岁,10毫克/千克青少年≥12岁.
- 临床试验是必要的,以验证这些较高的达普托米辛剂量在儿童群体.
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