Page 95 - 2019年9月第30卷第17期

蒙特卡洛模拟法在抗菌药物治疗ICU患者大肠埃希菌感染时初

始给药方案制订中的应用 Δ

姚欣凯 ，吴洪文 ，刘海林 ，凌宙贵 （1.广西医科大学附属第四医院药学部，广西 柳州 545005；2.重庆两江新
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1＊
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区第一人民医院药剂科，重庆 400015；3.广西医科大学附属第四医院呼吸与危重症医学科，广西 柳州
545005）
中图分类号 R969.3 文献标志码 A 文章编号 1001-0408（2019）17-2394-05
DOI 10.6039/j.issn.1001-0408.2019.17.18

摘 要 目的：为抗菌药物治疗重症加强护理病房（ICU）患者大肠埃希菌（Escherichia coli，E. coli）感染时初始给药方案的制订提
供参考。方法：基于CHINET中国细菌耐药监测网2016年发布的关于医院的E. coli耐药监测报告，收集全国19所三级甲等医院
标示为ICU病区临床分离的E. coli，选取对E. coli耐药率低于40％且临床实际工作中使用率较高的抗菌药物为研究对象，拟定模
拟给药方案，运用蒙特卡洛模拟法模拟不同给药方案对ICU病区“E. coli感染患者”中10 000“例”的临床疗效，以％ fT＞MIC＞50％
（哌拉西林他唑巴坦、头孢哌酮舒巴坦）、％ fT＞MIC＞40％（美罗培南）、fcmax/MIC＞10（阿米卡星）为目标阈值，计算“群体患者”达到
目标阈值的累积响应百分率（CFR），最佳给药方案要求CFR≥90％。并与临床ICU病区275例病例进行对照。结果：确定了4种抗菌
药物，分别为头孢哌酮舒巴坦、哌拉西林他唑巴坦、美罗培南和阿米卡星；共模拟了16种给药方案，其中头孢哌酮舒巴坦1种“3.0 g，
q8 h”，哌拉西林他唑巴坦3种“2.25 g，q6 h”“3.375 g，q8 h”“3.375 g，q6 h”，美罗培南2种“0.5 g，q8 h”“1.0 g ，q8 h”，阿米卡星3种
“0.4 g，q24 h”“0.6 g，q24 h”“0.8 g，q24 h”，其CFR均大于90％，均可作为初始给药方案。临床结果与模拟结果基本一致。结论：上
述哌拉西林他唑巴坦、头孢哌酮舒巴坦、美罗培南、阿米卡星给药方案均可作为ICU患者E. coli感染时的初始经验药物选择。
关键词 药动学；药效学；蒙特卡洛模拟；抗菌药物；大肠埃希菌；初始给药方案

Application of Monte Carlo Simulation Method in the Formulation of Primary Medication Regimen for
Antibacterial Drug Treatment of ICU Patients with Escherichia coli Infection
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YAO Xinkai ，WU Hongwen ，LIU Hailin ，LING Zhougui（1.Dept. of Pharmacy，the 4th Affiliated Hospital of
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Guangxi Medical University，Guangxi Liuzhou 545005，China；2.Dept. of Pharmacy，the First People’s
Hospital of Chongqing Liangjiang New District，Chongqing 400015，China；3.Dept. of Respiratory and Critical
Care Medicine，the 4th Affiliated Hospital of Guangxi Medical University，Guangxi Liuzhou 545005，China）
ABSTRACT OBJECTIVE：To provide reference for the formulation of primary medication regimen for antibacterial drug
treatment of ICU patients with Escherichia coli infection. METHODS：Based on the surveillance report on E. coli resistance in
hospitals issued by CHINET China bacterial drug resistance surveillance network in 2016，19 third class A hospitals in China were
collected as E. coli clinically isolated from ICU wards. Antibiotics with resistance rate of less than 40％ to E. coli and with high
utilization rate in clinical practice were selected as the research objects，and a simulated drug delivery scheme was formulated.
Monte Carlo simulation method was used to simulate the clinical effect of different dosage regimens on 10 000 cases among
“patients with E. coli infection”in ICU wards. The target thresholds were ％fT＞MIC＞50％（piperacillin/tazobactam，cefoperazone/
sulbactam），％ fT＞MIC＞40％（meropenem），fcmax/MIC＞10（amikacin）. The cumulative response percentage（CFR）to the target
threshold requires that CFR be greater than 90％ for the optimal regimen. The results were compared with those of 275 clinical ICU
pationts. RESULTS：Four antibiotics were identified，namely cefoperazone/sulbactam，piperacillin/tazobactam，meropenem and
amikacin；sixteen medication regimen were simulated，including 1 kind of cefoperazone/sulbactam“3.0 g，q8 h”；3 kinds of
piperacillin/tazobactam“2.25 g， q6 h”“3.375 g，q8 h”and“3.375 g，q6 h”；2 kinds of meropenem“0.5 g，q8 h”“1.0 g，q8
h”；3 kinds of amikacin“0.4 g，q24 h”“0.6 g，q24 h”and“0.8 g，q24 h”. Their CFR values were higher than 90％，all of them
could be regarded as primary medication regimen. The clinical results were basically consistent with the simulation results.
CONCLUSIONS：Above medication regimen of piperacillin/tazobactam，cefoperazone/sulbactam，meropenem and amikacin can be
used as initial empirical drug selection for patients with E. coli
Δ 基金项目：广西科技计划项目（No.桂科 AB16380152）；柳州市
科技计划项目（No.2018BJ10509） infection in ICU.
＊主管药师，硕士。研究方向：医院药学和临床药学。电话： KEYWORDS Pharmacokinetics；Pharmacodynamics；Monte
0772-2127952。E-mail：578275657@qq.com Carlo simulation； Antibiotics； Escherichia coli； Primary
# 通信作者：主任医师，博士。研究方向：呼吸与危重症医学。电 medication regimen
话：0772-3120747。E-mail：lzg228@163.com

·2394 · China Pharmacy 2019 Vol. 30 No. 17 中国药房 2019年第30卷第17期