应用蒙特卡罗模拟优化亚胺培南在重症病人鲍曼不动杆菌感染中的给药方案  

Evaluation of imipenem dosing regimen for Acinetobacter Baumannii infection in critically ill patients using monte carlo simulation

作　　者：孙璐 孟丹丹 董海燕[1] SUN Lu;MENG Dandan;DONG Haiyan(Department of Pharmacy,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an,Shaanxi 710061,China)

机构地区：[1]西安交通大学第一附属医院药学部,陕西西安710061

出　　处：《安徽医药》2022年第10期2106-2110,I0005,共6页Anhui Medical and Pharmaceutical Journal

基　　金：西安市科技计划项目[20YXYJ0001(5)];西安交通大学第一附属医院基金(2018MS-13、2019ZYTS-01)。

摘　　要：目的优化亚胺培南在接受连续肾脏替代治疗(continuous renal replacement therapy,CRRT)和非CRRT重症病人鲍曼不动杆菌感染中的给药方案。方法依据从1989年1月至2019年12月检索到的亚胺培南在重症病人中的药动学数据,分别以血浆中游离药物浓度超过最低抑菌浓度(MIC)的时间比例(fT>MIC)和fT>4MIC为目标值,应用蒙特卡罗模拟法评估不同给药方案下CRRT病人及非CRRT病人的达标概率(PTA),探索最佳给药方案。结果以40%fT>4MIC为目标值,当MIC≤2 mg/L时,CRRT病人和非CRRT病人0.5 g、6小时/次,0.75 g、6小时/次,0.75 g、8小时/次,1 g、6小时/次和1 g、8小时/次的给药方案的PTA均能达到90%以上;当MIC为4 mg/L或8 mg/L时,CRRT病人和非CRRT病人1 g、6小时/次给药方案的PTA能达到90%以上。以100%fT>MIC为目标值,当MIC≤2 mg/L时,CRRT病人和非CRRT病人0.75 g、6小时/次和1 g、6小时/次的给药方案的PTA能达到90%以上;当MIC为4 mg/L或8 mg/L时,仅CRRT病人1 g、6小时/次给药方案的PTA能达到90%以上。结论对于鲍曼不动杆菌感染的CRRT重症病人,当MIC≤2 mg/L时,无论以40%fT>4MIC或100%fT>MIC为目标值,给予0.5 g、6小时/次即可获得较高PTA(>90%);与CRRT重症病人相比,非CRRT重症病人鲍曼不动杆菌感染时则需要提高亚胺培南剂量以期达到最佳疗效。Objective To optimize the dosage regimens of Imipenem using Monte Carlo simulation in critically ill patients undergoing continuous renal replacement therapy(CRRT)and non-CRRT in Acinetobacter baumannii infections.Methods Based on the pharmacokinetic data of imipenem in critically ill patients retrieved from January 1989 to December 2019,the time ratio of free drug concentration over minimum inhibitory concentration(MIC)in Plasma f T>MIC and f T>4MIC was the target value.The PTA of CRRT patients and non-CRRT patients under different dosing regimens was evaluated by Monte Carlo method,and the best dosing regimen was explored.Results Taking 40%fT>4MIC as the target value,when MIC≤2 mg/L,the PTA of administration regimen(0.5 g q6h,0.75 g q6h,0.75 g q8h,1 g q6h and 1 g q8h)for CRRT patients and non-CRRT patients could reach more than 90%.When MIC=4 mg/L or 8 mg/L,the PTA of administration regimen(1 g q6h)for CRRT patients and non-CRRT patients could reach more than 90%.Taking 100%fT>MIC as the target value,when MIC≤2 mg/L,the PTA of administration regimen(0.75 g q6h and 1 g q6h)for CRRT patients and non-CRRT patients could reach more than 90%;when MIC=4 mg/L or 8 mg/L,only the PTA of 1 g q6h administration regimen for CRRT patients can reach more than 90%.Conclusion For critically ill CRRT patients with Acinetobacter baumannii infection,when MIC≤2mg/L,whether 40%fT>MIC or 100%fT>MIC is used as the target value,both for safety,0.5g q6h can achieve effective treatment;compared with severe patients with CRRT,non-severe patients with Acinetobacter baumannii infection need to increase the dose of Imipenem in order to achieve the best effect.

关 键 词：亚胺培南 重症病人 蒙特卡罗模拟 药动学/药效学 鲍曼不动杆菌 

分 类 号：R969.3[医药卫生—药理学]