蒙特卡罗模拟法评价和优化哌拉西林钠他唑巴坦的治疗方案

Evaluation and Optimizing of Therapeutic Regimen of Piperacillin Sodium Tazobactam by Monte-Carlo Simulation

目的:采用蒙特卡罗模拟法评价和优化重症加强护理病房患者常见革兰阴性菌感染应用哌拉西林钠他唑巴坦的治疗方案。方法:回顾性调查2017年中山市人民医院重症加强护理病房常见革兰阴性菌的细菌分布及耐药性监测报告,按照2016年美国临床实验室标准化协会标准,对大肠埃希菌、肺炎克雷伯菌和铜绿假单胞菌的最低抑菌浓度设置为离散均匀分布,确定哌拉西林钠他唑巴坦6种治疗方案,运用药动学/药效学(PK/PD)模型和蒙特卡罗模拟10 000例"真实患者"的目标获得概率(PTA),优化出3种常见抗革兰阴性菌最佳初始给药方案。结果:对于重症加强护理病房患者大肠埃希菌和肺炎克雷伯菌感染,"哌拉西林钠他唑巴坦3.375 g,每6 h给药1次"和"哌拉西林钠他唑巴坦4.5 g,每6 h给药1次"两种给药方案的PTA均>90%;而对于铜绿假单胞菌感染,只有"哌拉西林钠他唑巴坦4.5 g,每6 h给药1次"给药方案的PTA>90%;最低抑菌浓度(MIC)和半衰期是影响治疗效果的主要因素,且半衰期为正相关,MIC为负相关。结论:采用哌拉西林钠他唑巴坦经验治疗重症加强护理病房患者大肠埃希菌和肺炎克雷伯菌感染时,建议选择"3.375 g,每6 h给药1次"方案;而铜绿假单胞菌感染时,则推荐选择"4.5 g,每6 h给药1次"方案;目标治疗则应根据各病原菌MIC调整给药方案。

OBJECTIVE:Monte-Carlo simulation was adopted to evaluate and optimize the therapeutic regimen of piperacillin sodium tazobactam in treatment of common gram-negativebacterial infectionin ICU.METHODS:The distribution and drug-resistance monitoring reports of common gram-negative bacteria in ICU of Zhongshan People's Hospital in 2017 were retrospectively investgated,according to related criteria of 2016 American Association of Clinical Laboratory Standard,the minimum inhibitory concentrations(MIC)of Escherichia coli,Klebsiella pneumoniae and Pseudomonas aeruginosa were set as discrete distribution,and 6 therapeutic regimens of piperacillin sodium tazobactam were determined.Using pharmacokinetic/pharmacodynamic(PK/PD)model and Monte-Carlo to simulate probability of target attainment(PTA)of 10 000"real patients",so as to optimize three optimal initial dosage regimens of common gram-negative bacteria.RESULTS:For patients with E.coli and K.pneumoniae infection in ICU,both the PTA of the dosage regimens of"3.375 g of piperacillin sodium tazobactam for every 6 h"and"4.5 g of piperacillin sodium tazobactam for every 6 h"were >90%;while for P.aeruginosa infection,the PTA of only the dosage regimen of"4.5 g of piperacillin sodium tazobactam for every 6 h"were >90%;MIC and half-life period were the main factors affecting the efficacy,the half-life was positively correlated and the MIC was negatively correlated.CONCLUSIONS:When piperacillin sodium tazobactam is adopted in treatment of E.coli and K.pneumoniae infection in ICU,it is recommended to choose the therapeutic regimen of"3.375 g for every 6 h";while for P.aeruginosa infection,it is recommended to choose"4.5 g for every 6 h";and target treatment should adjust the dosage regimen according to the MIC value of each pathogen.