头孢他啶阿维巴坦治疗多重耐药革兰阴性菌感染的真实世界研究  

Real-world study of ceftazidime-avibactam in the treatment of multidrug-resistant gram-negative bacterial infections

作　　者：姜道利 丑晓华 刘志东 李薇 张波 许桑 谈德斐 方翼[4] 吕冬梅 王涛 JIANG Daoli;CHOU Xiaohua;LIU Zhidong;LI Wei;ZHANG Bo;XU Sang;TAN Defei;FANG Yi;LV Dongmei;WANG Tao(Department of Pharmacy,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221004,Jiangsu,China;Department of Pharmacy,Yixing People's Hospital,Yixing 214200,Jiangsu,China;Department of Pharmacy,the First People's Hospital of Zhenjiang,Zhenjiang 212000,Jiangsu,China;Phase I clinical trial center,Peking University People's Hospital,Beijing 100044,China)

机构地区：[1]徐州医科大学附属医院药学部,徐州221004 [2]宜兴市人民医院药学部,宜兴214200 [3]镇江市第一人民医院药学部,镇江212000 [4]北京大学人民医院Ⅰ期临床试验中心,北京100044

出　　处：《中国临床药理学与治疗学》2023年第9期1008-1017,共10页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目(82003866);江苏省研究型医院学会精益化用药-石药专项科研基金资助项目(JY202036);徐州市重点研发计划(社会发展)项目(KC22257)。

摘　　要：目的:描述与评价头孢他啶阿维巴坦(ceftazidime-avibactam,CZA)治疗多重耐药革兰阴性菌(multidrug-resistant gram-negative bacteria,MDR-GNB)感染患者的临床特征、治疗管理与临床结局。方法:选取2019年9月至2021年12月在徐州医科大学附属医院住院治疗的患者进行回顾性的队列研究。连续接受CZA治疗≥72 h的成人患者符合纳入条件。主要结局是临床失败,定义为30 d全因死亡、微生物学疗效失败和/或在接受CZA治疗期间未能解决或改善感染迹象和症状的综合因素。结果:共计对198例MDR-GNB感染患者的数据进行描述与评估,其中耐碳青霉烯类肠杆菌科细菌(carbapenem-resistant Enterobatceriaceae,CRE)队列132例,假单胞菌属(Pseudomonas spp.)队列66例。主要感染部位以肺部感染(92.42%)、腹腔感染(10.61%)、颅内感染(10.61%)最为常见,血培养阳性63例(31.82%)。临床结局失败61例(30.81%),30 d全因死亡33例(16.67%),30 d微生物疗效失败11例(5.56%)。体质量指数(BMI)、急性生理学及慢性健康状况评分(APACHEⅡ)、多种病原微生物感染与临床结局失败呈正相关(矫正OR 1.109,95%CI 1.017,1.209;矫正OR 1.071,95%CI 1.015,1.129;矫正OR2.844,95%CI 1.391,5.814)。入院后48 h内启动CZA治疗与临床结局失败呈负相关(矫正OR0.424,95%CI 0.205,0.879)。共15例患者出现了与CZA可能相关的不良反应,其中皮疹2例,恶心呕吐6例,抗生素相关性腹泻7例。结论:CZA能够用于治疗一系列MDR-GNB导致的感染,包括Pseudomonas spp.和CRE。AIM:To describe and evaluate the clinical characteristics,treatment management and clinical outcomes of ceftazidime-avibactam(CZA)in the treatment of patients with multidrug-resistant gram-negative bacterial(MDR-GNB)infections.METHODS:A retrospective cohort study was performed on patients hospitalized in the Affiliated Hospital of Xuzhou Medical University from September 2019 to December 2021.Adult patients who received CZA for≥72 hours consecutively were eligible for inclusion.The primary outcome was clinical failure,defined as a composite of 30-day all-cause mortality,microbiological failure and/or failure to resolve or improve signs and symptoms of infection during treatment with CZA.RESULTS:A total of 198 patients with MDR-GNB infections were described and evaluated,including 132 in the carbapenem-resistant Enterobatceriaceae(CRE)cohort and 66 in the Pseudomonas spp.cohort.The main infection sites were lung infection(92.42%),abdominal infection(10.61%),and intracranial infection(10.61%),among which 63 patients(31.82%)were positive for blood culture.Clinical failure,30-day all-cause mortality and microbiological failure occurred in 61(30.81%),33(16.67%)and 11(5.56%)patients,respectively.Body mass index(BMI),acute physiology and chronic health evaluation scoring system(APACHEⅡ)and polymicrobial infections were positively associated with clinical outcome failure[adjusted OR 1.109,95%CI 1.017,1.209;adjusted OR 1.071,95%CI 1.015,1.129;adjusted OR 2.844,95%CI 1.391,5.814],however,initiation of CZA within 48 hours of admission was protective(adjusted OR 0.424,95%CI 0.205,0.879).A total of 15 patients had adverse reactions possibly related to CZA,including 2 cases of rash,6 cases of nausea and vomiting,and 7 cases of antibiotic-related diarrhea.CONCLUSION:CZA can be used to treat infections caused by a range of MDR-GNB,including Pseudomonas spp.and CRE.

关 键 词：头孢他啶阿维巴坦 多重耐药革兰阴性菌 耐碳青霉烯类肠杆菌科细菌 假单胞菌属 

分 类 号：R969[医药卫生—药理学]