Epidemiology and Mechanisms of Ceftazidime-Avibactam Resistance in Gram-Negative Bacteria

作     者：Tingting Xu Yuqi Guo Yang Ji Baohong Wang Kai Zhou Tingting Xu;Yuqi Guo;Yang Ji;Baohong Wang;Kai Zhou

作者机构：Shenzhen Institute of Respiratory DiseasesShenzhen People’s Hospital&2nd Clinical Medical College of Jinan University&1st Affiliated Hospital of Southern University of Science and TechnologyShenzhen 518020China State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003China 

出 版 物：《Engineering》 (工程（英文）)

年 卷 期：2022年第8卷第4期

页      面：138-145页

核心收录：

学科分类：100208[医学-临床检验诊断学] 1002[医学-临床医学] 10[医学] 

基　　金：supported by the National Key Research and Development Program of China (2017YFC1200200) Major Infectious Diseases such as AIDS and Viral Hepatitis Prevention and Control Technology Major Projects (2018ZX10712-001) National Natural Science Foundation of China (81702045 and 81902030) Shenzhen Basic Research projects (JCYJ20190807144409307) 

主　　题：Ceftazidime-avibactam Resistance mechanism Carbapenem-resistant b-lactam/b-lactamase inhibitor 

摘      要：Carbapenem resistance presents a major challenge for the global public health network, as clinical infections caused by carbapenem-resistant organisms(CRO) are frequently associated with significant morbidity and mortality. Ceftazidime–avibactam(CAZ–AVI) is a novel cephalosporin/β-lactamase inhibitor combination offering an important advance in the treatment of CRO infections. CAZ–AVI has been reported to inhibit the activities of Ambler classes A, C, and some class D enzymes. However, bacterial resistance has been emerging shortly after the introduction of this combination in clinical use, with an increasing trend. Understanding these resistance mechanisms is crucial for guiding the development of novel treatments and aiding in the prediction of underlying resistance mechanisms. This review aims to systematically summarize the epidemiology of CAZ–AVI-resistant strains and recently identified resistance mechanisms of CAZ–AVI, with a focus on the production of β-lactamase variants, the hyperexpression of β-lactamases, reduced permeability, and overexpressed efflux pumps. The various mechanisms of CAZ–AVI resistance that have emerged within a short timescale emphasize the need to optimize the use of current agents, as well as the necessity for the surveillance of CAZ–AVI-resistant pathogens.