蒙特卡洛模拟评价和优化产超广谱β-内酰胺酶大肠埃希菌血流感染抗菌药物给药方案

Evaluations and optimization of antibacterial agents dose regimens of extended spectrum β-lactamases Escherichia coli bloodstream infection base upon Monte Carlo simulation

目的:评价和优化某院产超广谱β-内酰胺酶大肠埃希菌(ESBLs-EC)血流感染抗菌药物给药方案。方法:收集该院2019年产ESBLs-EC血流感染对亚胺培南西司他丁、哌拉西林钠他唑巴坦、头孢吡肟、头孢他啶和阿米卡星耐药监测报告,确定亚胺培南西司他丁、哌拉西林钠他唑巴坦、头孢吡肟、头孢他啶和阿米卡星治疗方案,根据各抗菌药物的药动学/药效学(PK/PD)模型,运用蒙特卡洛模拟(MCS)计算5种抗菌药物不同给药方案的达标概率(PTA)和累积反应分数(CFR),评价疗效和优化出最佳初始给药方案。结果:亚胺培南西司他丁1 g q12h、1 g q8h和1 g q6h,哌拉西林钠他唑巴坦4.5 g q8h和4.5 g q6h共5种给药方案的CFR≥90%,而头孢吡肟、头孢他啶和阿米卡星所有给药方案CFR均小于90%。结论:该院产ESBLs-EC血流感染时,经验选择可用亚胺培南西司他丁1 g q12h,哌拉西林钠他唑巴坦4.5 g q8h,不推荐头孢吡肟、头孢他啶和阿米卡星经验性治疗,临床经验性治疗与模拟结果基本一致,个体化治疗则应根据MIC值调整给药方案。

OBJECTIVE To evaluate and optimize antibacterial agents dose regimens of extended spectrum β-lactamases Escherichia coli(ESBLs-EC)bloodstream infection at a hospital. METHODS Surveillance reports were collected for ESBLs-EC bloodstream infection resistance to imipenem cilastatin,piperacillin tazobactam,cefepime,ceftazidime and amikacin of 2019 and their therapeutic regimens determined.According to the pharmacokinetics/pharmacodynamics(PK/PD)model of each antimicrobial drug,Monte-Carlo simulation(MCS)was utilized for calculating five different kinds of antimicrobial agent dosage regimen.The values of probability of target attainment(PTA)and cumulative fraction of response(CFR)were calculated.RESULTS CFR of imipenem cilastatin 1 g q12 h,1 g q8 h & 1 g q6 h,piperacillin tazobactam 4.5 g q8 h & 4.5 g q6 h,total 5 drug regimens were>90%.However,for cefepime,ceftazidime and amikacin,all dosage regimens of CFR were<90%.CONCLUSION When ESBLs-EC bloodstream infection occurs in a hospital,imipenem cilastatin1 g q12 h and piperacillin tazobactam 4.5 g q8 h regimens may be used empirically.And cefepime,ceftazidime and amikacin are not recommended for empirical treatment.Clinical empirical therapy is basically consistent with simulation results and target therapy should be adjusted according to minimum inhibitory concentration(MIC).