金属碳青霉烯酶的作用机制及其抑制剂研究进展

摘要

Carbapenems were considered as one of the last line of defense against serious infections caused by Gram-negative pathogens.In recent years,with the wide use of carbapenems in clinical practice and the spread of plasmid-mediated genes of resistance,the incidence of carbapenem-resistant isolates is increasing.The production of carbapenemases is the main cause of drug resistance.Metallo-carbapenemases,belonging to the B subclass of the carbapenemases,are the most versatile family of β-lactamases which are able to hydrolyze carbapenems and almost all other β-lactams,except for aztreonam.There are no effective inhibitors against metallo-carbapenemases for clinical use so far.The structures and catalytic mechanisms of metallo-carbapenemases and their inhibitors were reviewed in this paper.%碳青霉烯类抗生素是临床治疗革兰阴性菌感染的最后一道防线之一.近年来随着碳青霉烯类抗生素在临床的大量使用,以及耐药基因在质粒水平迅速传播,其耐药率逐年上升.造成耐药的原因主要是产生碳青霉烯酶,其中金属碳青霉烯酶属于B类碳青霉烯酶,可以水解除单环β-内酰胺类抗生素之外的几乎所有β-内酰胺类抗生素,目前尚无有效的抑制剂上市.本文就金属碳青霉烯酶的种类结构,作用机制及其抑制剂3个方面作简要综述.