应用蒙特卡洛模拟评价和优化左氧氟沙星的给药方案

Optimizing dosage regimen of levofloxacin against Escherichia coli based on Monte Carlo simulation

目的评价不同单剂量喹诺酮类抗菌药物左氧氟沙星不同的给药方案(250、500、750 mg,1次/d)对尿路感染大肠埃希菌药效学。方法收集2018年3至5月温州医科大学附属第三医院采用琼脂稀释法测定临床分离的121株致尿路感染大肠埃希菌的最低抑菌浓度(MIC),收集尿液左氧氟沙星的药动学资料,应用蒙特卡洛模拟方法分析左氧氟沙星的药效学。结果250、500、750 mg剂量下左氧氟沙星治疗药效学累积反应分数(CFR)分别为63%、78%、87%。防突变药效学CFR分别为58%、68%、79%。250、500、750 mg剂量下获得治疗药效学目标90%PTA时细菌MIC值分别为16、32、64μg/ml,90%防突变浓度药效学目标时细菌MIC分别为8、16、16μg/ml。结论在本地区250、500、750 mg剂量左氧氟沙星治疗大肠埃希菌引起的尿路感染均不能获得90%的CFR,但750 mg剂量左氧氟沙星已经比较接近最佳的给药方案。

Objective To evaluate and optimize the dose regime of levofloxacin against urinary tract infection of Escherichia coli(E.coli)by using Monte Carlo simulation.Methods The minimum inhibitory concentration(MIC)of 121 strains E.coli isolated from patients with urinary tract infection was determined by agar dilution method.The pharmacokinetics of levofloxacin in urine were investigated and the pharmacodynamics of levofloxacin were analyzed by Monte Carlo simulation method.Results The cumulative fraction of response(CFR)of pharmacodynamics for levofloxacin at 250,500 and 750 mg was 63%,78%and 87%,the CFR of anti-mutation pharmacodynamics was 58%,68%and 79%,respectively.At levofloxacin doses of 250,500,750 mg,the bacterial MIC value for 90%pobability of target attainment(PTA)of pharmacodynamics was 16,32,64μg/ml,while the bacterial MIC value for 90%PTA of mutant prevention concentration pharmacodynamics was 8,16,16μg/ml,respectively.Conclusion In this region levofloxacin at dose of 250,500,750 mg cannot obtain 90%of the best dosage regimen in treatment of urinary tract E.coli infections,but 750 mg levofloxacin is close to the best dosing mode.