3种碳青霉烯类药物联合头孢哌酮钠舒巴坦钠对泛耐药鲍曼不动杆菌感染的PK/PD研究  

Pharmacokinetics/pharmacodynamics of three carbapenems combined with cefoperazone sodium and sulbactam sodium against extensively drug resistant Acinetobacter baumannii infection

作　　者：许亚洲 石祥奎 曹加 刘杰[3] 刘莹 XU Ya-zhou;SHI Xiang-kui;CAO Jia;LIU Jie;LIU Ying(Department of Pharmacy,Xuzhou Maternity and Child Health Care Hospital,Xuzhou Jiangsu 221009;Department of Pharmacy,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029;Department of Laboratory Medicine,Xuzhou Maternity and Child Health Care Hospital,Xuzhou Jiangsu 221009)

机构地区：[1]徐州市妇幼保健院药事科,江苏徐州221009 [2]南京医科大学第一附属医院药学部,南京210029 [3]徐州市妇幼保健院检验科,江苏徐州221009

出　　处：《中南药学》2023年第11期3051-3057,共7页Central South Pharmacy

基　　金：江苏省研究型医院学会精益化用药-石药专项科研基金项目(No.JY202026)。

摘　　要：目的探讨亚胺培南(IMP)、美罗培南(MEN)、比阿培南(BMP)3种碳青霉烯类与头孢哌酮钠舒巴坦钠(CFS)单用和联合用药对泛耐药鲍曼不动杆菌(XDR-AB)的体外抑菌作用,通过蒙特卡罗模拟评价筛选最佳给药方案。方法分离收集54株XDR-AB,基于微量肉汤稀释法测定单独及联合用药的最低抑菌浓度值(MIC),上计算抑菌浓度指数(FIC),结合药动学/药效学(PK/PD)参数,通过蒙特卡罗模拟对治疗方案进行优化。结果联合用药主要显示为协同作用和相加作用,与单用药相比,联合用药的累积抑菌百分率曲线左移。蒙特卡罗模拟结果显示,在限定用药剂量范围内通过延长静脉滴注时间,5种亚胺培南和2种比阿培南联合用药方案可获得有效的累积反应分数(CFR)目标值;在联合用药方案中,延长CFS静脉滴注时间并使舒巴坦钠用量达到9 g·d^(-1)可获得有效的CFR目标值。结论体外研究结果显示,CFS联合3种碳青霉烯类对XDR-AB有效,但蒙特卡罗模拟显示需增加其给药次数、延长静脉滴注时间并加大用药剂量对XDR-AB才可获得有效的CFR目标值。Objective To evaluate three carbapenems(imipenem,meropenem,and biapenem)used alone or in combination with cefoperazone sodium and sulbactam sodium(CFS)against extensively drug resistant Acinetobacter baumannii(XDR-AB).Monte Carlo simulation(MCS)was used to evaluate the optimal dosing regimen.Methods Totally 54 isolates of XDR-AB were collected.The minimum inhibitory concentration(MIC)was tested by agar dilution method and the fractional inhibitory concentration(FIC)caculated.According to the MIC and pharmacokinetic/pharmacodynamic(PK/PD)parameters,dosing regimens were optimized by MCS.Results Carbapenems in combination with CFS mainly showed synergistic effect and additive effect.Cumulative bacteriostatic percentage curve of drugs in combination obviously moved to the left compared with drugs used alone.Within maximum daily dose,five imipenem and two biapenem regimens in combination with prolonged intravenous infusion time obtained cumulative fraction of response value(CFR)by MCS.In addition,increased dose of CFS in combination with sulbactam sodium(9 g·d^(-1))with prolonged intravenous infusion time obtained effective CFR.Conclusion Prolonged intravenous infusion time,high dose and increased frequency of administration result in effective CFRs for carbapenems in combination with CFS against XDR-AB.

关 键 词：碳青霉烯类 头孢哌酮钠舒巴坦钠 蒙特卡罗模拟 泛耐药鲍曼不动杆菌 

分 类 号：R969.3[医药卫生—药理学]