应用药动学/药效学模型结合蒙特卡洛模拟评价和优化产超广谱β-内酰胺酶肺炎克雷伯菌抗菌药物给药方案  

Application of PK/PD model combined with Monte-carlo simulation to estimate and optimize dosage regimens for extended spectrum β-lactamases klebsiella pneumoniae infection

作　　者：刘峰[1] 邓贵新[1] 唐蕾[1] 刘锐锋[1] LIU Feng;DENG Gui-xin;TANG Lei;LIU Rui-feng(Zhongshan City People's Hospital,Zhongshan 528403,China)

机构地区：[1]中山市人民医院,中山528403

出　　处：《中国新药杂志》2020年第12期1434-1440,共7页Chinese Journal of New Drugs

基　　金：广东省中山市科技局资助项目(2019B1076)。

摘　　要：目的:评价和优化我院产超广谱β-内酰胺酶(extended spectrumβ-lactamases,ESBLs)肺炎克雷伯菌感染抗菌药物给药方案。方法:收集我院2018年产ESBLs肺炎克雷伯菌对亚胺培南西司他丁、哌拉西林钠他唑巴坦、头孢吡肟、阿米卡星和左氧氟沙星耐药监测报告,确定这5种抗菌药物的治疗方案,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(Monte-carlo simulation,MCS)计算5种抗菌药物不同给药方案的达标概率(probability of target attainment,PTA)和累积反应分数(cumulative fraction of response,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0.5 g q12h,0.5 g q8h和0.5 g q6h,哌拉西林钠他唑巴坦4.5 g q6h,头孢吡肟2 g q8h,阿米卡星0.7 g qd,0.8 g qd和0.9 g qd共8种给药方案的CFR≥90%,而左氧氟沙星所有给药方案CFR均<90%。结论:我院产ESBLs肺炎克雷伯菌感染时,经验选择可用亚胺培南西司他丁0.5 g q12h、哌拉西林钠他唑巴坦4.5 g q6h,头孢吡肟2 g q8h和阿米卡星0.7 g qd,不推荐左氧氟沙星首选经验性治疗,临床经验性治疗与模拟结果基本一致,目标治疗则应根据最低抑菌浓度(minimum inhibitory concentration,MIC)值调整给药方案。Objective:To estimate and optimize the dosage regimens for extended spectrumβ-lactamases(ESBLs)Klebsiella pneumoniae infection in our hospital.Methods:The surveillance reports of ESBLs Klebsiella pneumoniae resistance to imipenem cilastatin,piperacillin tazobactam,cefepime,amikacin and levofloxacin in our hospital in 2018 were collected.The dosage regimens of imipenem cilastatin,piperacillin tazobactam,cefepime,amikacin and levofloxacin determined according to the pharmacokinetics/pharmacodynamics(PK/PD)model of each antimicrobial drug.Monte-carlo simulation(MCS)was used to calculate the probability of target attainment(PTA)and cumulative fraction of response(CFR)of dosage regimens of these 5 antimicrobial drugs,evaluate the efficacy and optimize the initial dosage regimen.Results:The CFRs of imipenem cilastatin 0.5 g q12 h,0.5 g q8 h and 0.5 g q6 h,piperacillin tazobactam 4.5 g q6 h,cefepime 2 g q8 h,amikacin 0.7 g qd,0.8 g qd and 0.9 g qd,were all more than 90%,but for levofloxacin,the CFRs of all dosage regimens were less than 90%.Conclusion:When ESBLs Klebsiella pneumoniae infection occurs in our hospital,imipenem cilastatin 0.5 g q12 h,piperacillin tazobactam 4.5 g q6 h,cefepime 2 g q8 h and amikacin 0.7 g qd regimens can be used as an empirical treatment option,while levofloxacin is not recommended for empirical treatment.The clinical empirical therapy is basically consistent with the simulation results,and the target therapy should be adjusted according to the minimum inhibitory concentration(MIC).

关 键 词：蒙特卡洛模拟 产超广谱β-内酰胺酶肺炎克雷伯菌 给药方案 

分 类 号：R978.1[医药卫生—药品]