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头孢他啶/阿维巴坦耐药的细菌的分子机制。

Molecular mechanisms underlying bacterial resistance to ceftazidime/avibactam.

机构信息

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China.

出版信息

WIREs Mech Dis. 2022 Nov;14(6):e1571. doi: 10.1002/wsbm.1571. Epub 2022 Jul 26.

Abstract

Ceftazidime/avibactam (CAZ/AVI), a combination of ceftazidime and a novel β-lactamase inhibitor (avibactam) that has been approved by the U.S. Food and Drug Administration, the European Union, and the National Regulatory Administration in China. CAZ/AVI is used mainly to treat complicated urinary tract infections and complicated intra-abdominal infections in adults, as well as to treat patients infected with Carbapenem-resistant Enterobacteriaceae (CRE) susceptible to CAZ/AVI. However, increased clinical application of CAZ/AVI has resulted in the development of resistant strains. Mechanisms of resistance in most of these strains have been attributed to bla mutations, which lead to amino acid substitutions in β-lactamase and changes in gene expression. Resistance to CAZ/AVI is also associated with reduced expression and loss of outer membrane proteins or overexpression of efflux pumps. In this review, the prevalence of CAZ/AVI-resistance bacteria, resistance mechanisms, and selection of detection methods of CAZ/AVI are demonstrated, aiming to provide scientific evidence for the clinical prevention and treatment of CAZ/AVI resistant strains, and provide guidance for the development of new drugs. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.

摘要

头孢他啶/阿维巴坦(CAZ/AVI)是一种已获美国食品药品监督管理局、欧盟和中国国家药品监督管理局批准的头孢他啶与新型β-内酰胺酶抑制剂(阿维巴坦)的复方制剂。CAZ/AVI 主要用于治疗成人复杂性尿路感染和复杂性腹腔内感染,以及治疗对 CAZ/AVI 敏感的耐碳青霉烯类肠杆菌科(CRE)感染的患者。然而,CAZ/AVI 的临床应用增加导致了耐药菌株的出现。这些耐药菌株的大多数耐药机制归因于 bla 基因突变,导致β-内酰胺酶的氨基酸取代和基因表达的变化。CAZ/AVI 的耐药性也与外膜蛋白的表达减少或缺失或外排泵的过度表达有关。本综述阐述了 CAZ/AVI 耐药菌的流行情况、耐药机制以及 CAZ/AVI 检测方法的选择,旨在为 CAZ/AVI 耐药株的临床防治提供科学依据,并为新药的开发提供指导。本文属于以下分类:传染病>分子和细胞生理学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dc5/9788277/b707f228e906/WSBM-14-e1571-g002.jpg

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