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中国临床药理学与治疗学 ›› 2023, Vol. 28 ›› Issue (9): 1008-1017.doi: 10.12092/j.issn.1009-2501.2023.09.006

• 临床药理学 • 上一篇    下一篇

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

姜道利1,丑晓华1,刘志东1,李  薇1,张  波1,许  桑2,谈德斐3,方  翼4,吕冬梅1,王  涛1   

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

  • 收稿日期:2023-03-14 修回日期:2023-07-27 出版日期:2023-09-26 发布日期:2023-09-25
  • 通讯作者: 王涛,女,博士,主任药师,副教授,研究方向:药物基因组学与个体化用药。 Tel:0516-85806335 E-mail:misswt2011@126.com
  • 作者简介:姜道利,男,硕士研究生,讲师,副主任药师,研究方向:抗菌药物合理应用与个体化用药。 Tel:0516-85806336 E-mail:jiangdoali869@163.com
  • 基金资助:
    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)

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

JIANG Daoli1, CHOU Xiaohua1, LIU Zhidong1, LI Wei1, ZHANG Bo1, XU Sang2, TAN Defei3, FANG Yi4, LV Dongmei1, WANG Tao1   

  1. 1Department of Pharmacy, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, Jiangsu, China; 2Department of Pharmacy, Yixing People's Hospital, Yixing 214200, Jiangsu, China; 3Department of Pharmacy, the First People's Hospital of Zhenjiang, Zhenjiang 212000, Jiangsu, China; 4Phase I clinical trial center, Peking University People's Hospital, Beijing 100044, China
  • Received:2023-03-14 Revised:2023-07-27 Online:2023-09-26 Published:2023-09-25

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(APACHE Ⅱ)、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OR 2.844,95%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OR 0.424,95%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。

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

Abstract:

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 (APACHE Ⅱ) 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.

Key words: ceftazidime-avibactam, multidrug-resistant gram-negative bacterial, carbapenem-resistant enterobatceriaceae, Pseudomonas spp

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