应用蒙特卡洛模拟法优化利奈唑胺、替考拉宁和万古霉素在ICU患者治疗MRSA感染的给药方案

Optimizing the dosage regimens of linezolid,teicoplanin and vancomycin against MRSA infection in ICU patients based on Monte Carlo simulation

目的根据抗菌药物的药动学/药效学基本原理,应用蒙特卡洛模拟法优化利奈唑胺、替考拉宁和万古霉素治疗MRSA感染的给药方案。方法从已发表文献中获得利奈唑胺、替考拉宁和万古霉素在重症监护病房(ICU)患者中的药动学参数,从ECUST网站获得耐甲氧西林金黄色葡萄球菌(MRSA)对3种药物最低抑菌浓度值的分布。采用蒙特卡洛模拟法计算不同给药方案的目标获得概率和累积反应分数。结果收集的数据表明,利奈唑胺、替考拉宁和万古霉素在ICU患者中的药动学参数变化差异大。经模拟分析,利奈唑胺、替考拉宁、万古霉素3种药物分别以600mg/bid、500mg/qd、750mg/bid静脉输注的给药方案,对MRSA的治疗是合理的。同时临床上应根据MRSA病原菌对药物的敏感性调整给药方案。结论利用抗菌药物PK/PD基本原理结合蒙特卡洛模拟法,可优化利奈唑胺、替考拉宁和万古霉素用于MRSA经验治疗的给药方案,为临床提供参考。

Objective Based on the principle of pharmacokinetics/pharmacodynamics for antibiotics, the study was to optimize dosage regimens of linezolid, teicoplanin and Vancomycin in MRSA-infected patients with Monte Carlo simulation（MCS）. Methods Pharmacokinetics parameters of linezolid, teicoplanin and vancomycin in intensive care units＇ （ICU） patients collected from published literature. The distribution of minimal inhibitory concentrations of linezolid, teicoplanin and vancomycin for MRSA collected from ECUST website. Monte Carlo simulation was used to obtain the probability of target attainment and cumulative fraction of response of different dosage regimens. Results Based on the data collected, the pharmacokinetics of linezolid, teicoplanin and vancomycin in ICU patients shown a large variability. After optimizing the dosage regimens with MCS, the recommended dosage regimen of linezolid is 600mg/bid for MRSA-infected patients. For teicoplanin, the recommended dosage regimen is 500mg/qd and for Vancomycin, 750mg/bid. Additionally, dose-adjustment strategy that based on the susceptibility of MRSA should be carried during the treatment. Conclusions The pharmacokinetic/pharmacodynamics principle of antibacterial agents combined with MCS is an effective method to optimize the dosage regimens of linezolid, teicoplanin and vancomycin for the experience therapy of MRSA-infected patients. The related results are intelligible reference to the clinical.