万古霉素、哌拉西林/他唑巴坦、美罗培南在危重症患者中TDM靶值和PK/PD靶值的影响因素分析及微生物疗效分析  

Influencing factors of TDM target and PK/PD target attaintment for vancomycin,piperacillin/tazobactam and meropenem in critically ill patients and analysis of microbial efficacy

作　　者：董育珠 陶丽 韩鹃 廉衡 杜倩 张雷 DONG Yuzhu;TAO Li;HAN Juan;LIAN Heng;DU Qian;ZHANG Lei(Department of Pharmacy,The Third Affiliated Hospital of Chongqing Medical University,Chongqing 401120,China;Department of Emergency and Critical Care Center,The Third Affiliated Hospital of Chongqing Medical University,Chongqing 401120,China;Shenzhen BGI Co.Ltd.,Guangdong Shenzhen 518000,China)

机构地区：[1]重庆医科大学附属第三医院药剂科,重庆401120 [2]重庆医科大学附属第三医院急诊与重症医学中心,重庆401120 [3]深圳华大基因股份有限公司,广东深圳518000

出　　处：《中国医院药学杂志》2023年第20期2307-2312,共6页Chinese Journal of Hospital Pharmacy

基　　金：重庆市技术创新与应用发展专项(编号:cstc2019jscx-msxmX0195)。

摘　　要：目的:探讨影响万古霉素、哌拉西林/他唑巴坦、美罗培南3种药物治疗药物监测(therapeutic drug monitoring,TDM)靶值和药动学/药效学(pharmacokinetic/pharmacodynamic,PK/PD)靶值未达标的危险因素以及2种靶值和微生物疗效的关系,为精准用药提供科学依据。方法:纳入2021年3月至2022年3月接受万古霉素、哌拉西林/他唑巴坦、美罗培南中至少1种抗菌药物联合治疗的危重症患者。利用优化采样方案采集每位患者的3~4份血浆样本,借助非房室模型结合经典药动学理论计算PK/PD参数。采用多因素分析探究3种药物TDM靶值和PK/PD靶值未达标的相关危险因素。结果:共纳入接受万古霉素、哌拉西林/他唑巴坦或美罗培南治疗的25名危重症患者的96份血浆样本,共计151份血药浓度-时间数据。万古霉素、哌拉西林/他唑巴坦和美罗培南的谷浓度(trough concentration,Cmin)达标率低,分别为20.00%、22.22%和23.53%;万古霉素PK/PD靶值达标率、未达标率和超标率分别为20.00%、60.00%和20.00%。哌拉西林/他唑巴坦和美罗培南的PK/PD靶值达标率分别为11.11%和17.65%,未达标率分别高达88.89%和76.47%。影响因素探究发现肌酐清除率是影响3种抗菌药物Cmin和PK/PD靶值不达标的独立危险因素。细菌根除组患者的万古霉素Cmin[(15.329±7.522)mg·L^(-1)vs.(6.273±0.754)mg·L^(-1),P=0.019]和AUC0~24 h/MIC(578.47±413.86 vs.175.94±17.07,P=0.028)均显著高于细菌未根除组。结论:万古霉素、哌拉西林/他唑巴坦、美罗培南在危重症患者中的TDM靶值和PK/PD靶值达标率低,未达标率高,普遍存在低暴露和过暴露情况。提高TDM靶值和PK/PD靶值达标率均可能提高患者细菌根除率,因此十分有必要在此类患者中开展TDM,为精准给药提供参考。OBJECTIVE To explore the risk factors that affect the therapeutic drug monitoring(TDM)targets and pharmacokinetic/pharmacodynamic(PK/PD)targets of vancomycin,piperacillin/tazobactam,and meropenem,as well as the relationship between the two targets and microbial efficacy,in order to provide scientific basis for precise drug use.METHODS We included critically ill patients whom accepting TDM between March 2021 and March 2022.The optimized sampling regeim was used to collect 3-4 plasma samples from each patient,and the PK/PD index(AUC0-24 h/MIC and f%T>MIC)were calculated by non-compartmental model combined with classical pharmacokinetic theory.Multivariate analysis was used to explore the related risk factors for the TDM target PK/PD target attaintment not achieved.RESULTS A total of 151 plasma concentration-time data and a total of 96 plasma samples from 25 critically ill patients treated with vancomycin,piperacillin/tazobactam,and meropenem were included.The probability of Cminattaintment achieved for vancomycin,piperacillin/tazobactam and meropenem were as low as 20.00%,22.22%and 23.53%,respectively.The probability of PK/PD target attaintment achieved and not achieved for vancomycin was 20.00%,and 60.00%,20.00%AUC0-24 h/MIC was over than PK/PD target attaintment.The probability of PK/PD target attaintment achieved for piperacillin/tazobactam and meropenem was as low as 11.11%and 17.65%,respectively,and probability of PK/PD target attaintment not achieved was as high as 88.89%and 76.47%.The investigation of influencing factors found that the creatinine clearance on the sampling day was the only independent risk factor,affecting the Cmin and PK/PD attaintment not achieved for the three antibacterial drugs.The vancomycin Cmin[(15.329±7.522)mg·L^(-1)vs.(6.273±0.754)mg·L^(-1),P=0.019]and AUC0-24 h/MIC(578.47±413.86 vs.175.94±17.07,P=0.028)in the bacteria eradicated group were significantly higher than those in the bacteria persistence group.CONCLUSION Probability of TDM target and PK/PD target attaintment for va

关 键 词：万古霉素 哌拉西林/他唑巴坦 美罗培南 血药浓度 治疗药物监测靶值 药动学/药效学靶值 微生物疗效 

分 类 号：R969.3[医药卫生—药理学]