基于药代动力学/药效学模型联合蒙特卡洛模拟评价和优化亚胺培南/西司他丁在ICU的治疗方案  

Evaluation and Optimization of the Therapeutic Regimen by Applying Imipenem/Cilastatin in ICU Based on Pharmacokinetics and Pharmacodynamics with Monte Carlo Simulation

作　　者：陈烁 陈佳炜 黄培良 丁有奕 程龙飞 CHEN Shuo;CHEN Jiawei;HUANG Peiliang;DING Youyi;CHENG Longfei(Department of Pharmacy,Southern Medical University Chaozhou Central Hospital,Chaozhou,Guangdong 521000,China;Intensive Care Unit,Southern Medical University Chaozhou Central Hospital,Chaozhou,Guangdong 521000,China;Department of Laboratory,Southern Medical University Chaozhou Central Hospital,Chaozhou,Guangdong 521000,China)

机构地区：[1]南方医科大学附属潮州中心医院药学部,广东潮州521000 [2]南方医科大学附属潮州中心医院重症监护病房,广东潮州521000 [3]南方医科大学附属潮州中心医院检验科,广东潮州521000

出　　处：《今日药学》2022年第6期472-476,共5页Pharmacy Today

基　　金：潮州市科技计划自筹经费项目(2021ZC04)。

摘　　要：目的使用药代动力学/药效学模型联合蒙特卡洛模拟评价和优化某院ICU患者应用亚胺培南/西司他丁进行抗感染治疗的给药方案,为ICU合理使用亚胺培南/西司他丁提供参考。方法收集该院2019年1月~2021年12月重症监护病房中常见革兰氏阴性菌药敏试验报告,制订亚胺培南/西司他丁对4种革兰阴性菌治疗的6种给药方案,使用药代动学/药效学模型联合蒙特卡洛模拟的方法进行模拟,计算不同给药方案的达标概率和累积反应分数,优选出最佳的治疗方案。结果亚胺培南/西司他丁治疗4种革兰阴性菌,在“0.5 g q12h”的给药方案中,当最低抑菌浓度(MIC)=2μg·mL^(-1)和MIC=4μg·mL^(-1)时,达标概率(PTA)分别为80.38%和12.93%,均小于90%;在“1 g q12h”的给药方案中,当MIC=4μg·mL^(-1)时,PTA为79.46%。除以上3种情况之外,其他各用药方案,在不同的MIC下模拟的PTA都大于90%。对于鲍曼不动杆菌感染,亚胺培南/西司他丁“0.5 g q12h”和“1 g q12h”两种给药方案的累计反应分数(CFR)分别是44.26%和86.96%,均小于90%,其余4种给药方案的CFR均大于90%;对于铜绿假单胞菌的治疗,“0.5 g q12h”给药方案的CFR为55.41%,其余5种给药方案CFR均大于90%;对于肺炎克雷伯菌和大肠埃希菌感染,6种给药方案的CFR均大于90%。结论该院ICU重症感染患者在使用亚胺培南/西司他丁进行抗感染治疗时,对于鲍曼不动杆菌和铜绿假单胞菌可经验性使用“0.5 g q8h”给药方案;而对于肺炎克雷伯菌和大肠埃希菌感染,可经验性使用“0.5 g q12h”给药方案,目标性治疗则可根据具体MIC值进行给药方案调整,从而减少抗菌药物耐药性和药品不良反应的发生,降低患者的治疗费用。OBJECTIVE To evaluate and optimize the dosage regimen of using pharmacokinetics and pharmacodynamics(PK/PD)model combined with Monte Carlo Simulation for the anti-infection treatment in ICU patients so as to offer some reference in applying imipenem/cilastatin reasonably for ICU in a hospital.METHODS The drug sensitivity test reports of common Gram-negative bacteria in ICU in Chaozhou Central Hospital from January 2019 to December 2021 were collected to formulate 6 dosage regimens for 4 types of gram-negative bacteria.The model of PK/PD combined with Monte Carlo Simulation was used to calculate the standard reaching probability as well as accumulated reacting fraction in 6 dosage regimens for optimizing the best.RESULTS The probability of target attainment(PTA)were 80.38% and 12.93%respectively when minimun inhibitory concentration(MIC)=2μg·mL^(-1)and MIC=4μg·mL^(-1)in the“0.5 g q12h”regimen,which were less than 90%.In the“1 g q12h”regimen,when MIC=4μg·mL^(-1),The PTA was 79.46%.Except for the above three cases,other drug regimens,under different MIC simulation of PTA were greater than 90%.For acinetobacter baumannii infection,the cumulative fraction of response(CFR)of imipenem/cilastatin“0.5 g q12h”and“1 g q12h”were 44.26% and 86.96%,respectively,both less than 90%,and the CFR of the other 4 regimens were more than 90%.For the treatment of pseudomonas aeruginosa,the CFR of“0.5 g q12h”was 55.41%,the CFR of the other five regimens were more than 90%.And for the infection of klebsiella pneumoniae and escherichia coli,the CFR of the six regimens were more than 90%.CONCLUSION When using imipenem/cilastatin against the infection of ICU patients,the dosage regimen of antibiotic using 0.5 g per 8 hours can be adopted against the acinetobacter baumannii and pseudomonas aeruginosa.While dosage regimen of antibiotic using 0.5 g per 12 hours can be adopted against the klebsiella pneumoniae and escherichia coli.Dosage regimen can be adjusted according to the specific MICin targeting treatment,so as

关 键 词：亚胺培南/西司他丁 蒙特卡洛模拟 PK/PD参数 革兰阴性菌 

分 类 号：R969[医药卫生—药理学]