基于蒙特卡洛模拟评价与优化头孢他啶或美罗培南在类鼻疽病患者中的疗效  

Evaluation and optimization of the efficacy of ceftazidime or meropenem in melioidosis patients based on monte carlo simulation

作　　者：冯俊超 符策豪 梁柳茵 尚梅 FENG Junchao;FU Cehao;LIANG Liuyin;SHANG Mei(Department of Laboratory Medicine,Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou,Guangdong 510630,China)

机构地区：[1]中山大学附属第三医院检验科,广东广州510630

出　　处：《热带医学杂志》2024年第12期1747-1750,1755,共5页Journal of Tropical Medicine

基　　金：广东省自然科学基金区域联合项目(2020A1515110152);广州市科技计划项目(2024A04J4787)。

摘　　要：目的探讨头孢他啶和美罗培南两种抗生素不同给药方案在治疗类鼻疽伯克霍尔德菌感染中的疗效差异,为类鼻疽病的初始治疗方案提供参考。方法基于重症患者的群体药代动力学(PPK)参数和最小抑菌浓度(MIC),通过结合药动学/药效学(PK/PD)参数和蒙特卡洛模拟(MCS),分析头孢他啶(1g q12h、1g q8h、2g q12h、2g q8h)和美罗培南(0.5g q8h、1g q8h、1g q6h)的不同给药方案治疗类鼻疽伯克霍尔德菌的达标概率(PTA)和累积反应分数(CFR),将PTA≥90%和CFR≥90%的治疗方案作为治疗类鼻疽伯克霍尔德菌感染的最佳方案。结果在MIC_(50)条件下,即头孢他啶MIC值≤4μg/mL和美罗培南MIC值≤1μg/mL,两种药物的不同给药方案PTA值均超过90%;在MIC_(90)条件下,即头孢他啶MIC值≤16μg/mL和美罗培南MIC值≤2μg/mL,头孢他啶只有2g q8h给药方案PTA值超过90%,美罗培南的0.5g q8h、1g q8h和1g q6h给药方案PTA值均超过90%。头孢他啶的1g q8h和2g q8h给药方案CFR值超过90%,而美罗培南的0.5g q8h、1g q8h和1g q6h给药方案CFR值均超过90%。结论美罗培南的不同给药方案在治疗类鼻疽伯克霍尔德菌感染中表现出较高的PTA和CFR值,是更为理想的治疗方案;而头孢他啶的高剂量方案也显示出一定的疗效。Objective To explore the efficacy differences between different dosing regimens of two antibacterial drugs,ceftazidime and meropenem,in treating Burkholderia pseudomallei infections,and provide a reference for the initial treatment of melioidosis.Methods Based on the population pharmacokinetics(PPK)parameters and minimal inhibitory concentration(MIC)for critically ill patients,this study utilized pharmacokinetics/pharmacodynamics(PK/PD)parameter plus Monte Carlo simulation(MCS)to analyze the probability of target attainment probability of target attainment(PTA)and cumulative fraction of response(CFR)of different dosing regimens of ceftazidime(1g q12h,1g q8h,2g q12h,2g q8h)and meropenem(0.5g q8h,1g q8h,1g q6h)in treating Burkholderia pseudomallei.Treatment regimens with PTA≥90%and CFR≥90%were considered as the optimal for the treatment of Burkholderia pseudomallei infections.Results Under MIC_(50) conditions,that is,the value of ceftazidime MIC≤4μg/mL and meropenem MIC≤1μg/mL,the PTA values for all dosing regimens of both drugs exceeded 90%.Under MIC_(90) conditions,which means the value of ceftazidime MIC≤16μg/mL and meropenem MIC≤2μg/mL,only the 2g q8h regimen of ceftazidime had a PTA value exceeding 90%,while 0.5g q8h,1g q8h,and 1g q6h dosing regimens of meropenem had PTA values exceeding 90%.In terms of CFR,the 1g q8h and 2g q8h dosing regimens of ceftazidime had CFR values exceeding 90%,and CFR values for the meropenem regimens of 0.5g q8h,1g q8h,and 1g q6h were all exceeded 90%.Conclusions Meropenem's different dosing regimens showed higher PTA and CFR values,making it a more ideal treatment option for Burkholderia pseudomallei infections.High⁃dose regimens of ceftazidime also demonstrated certain efficacy.

关 键 词：类鼻疽伯克霍尔德菌 蒙特卡洛模拟 头孢他啶 美罗培南 PK/PD 

分 类 号：R754.3[医药卫生—皮肤病学与性病学]