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金属β-内酰胺酶:结构、功能、流行病学、治疗选择和研发管线。

Metallo-β-Lactamases: Structure, Function, Epidemiology, Treatment Options, and the Development Pipeline.

机构信息

Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom

National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, London, United Kingdom.

出版信息

Antimicrob Agents Chemother. 2020 Sep 21;64(10). doi: 10.1128/AAC.00397-20.

Abstract

Modern medicine is threatened by the global rise of antibiotic resistance, especially among Gram-negative bacteria. Metallo-β-lactamase (MBL) enzymes are a particular concern and are increasingly disseminated worldwide, though particularly in Asia. Many MBL producers have multiple further drug resistances, leaving few obvious treatment options. Nonetheless, and more encouragingly, MBLs may be less effective agents of carbapenem resistance , under zinc limitation, than Owing to their unique structure and function and their diversity, MBLs pose a particular challenge for drug development. They evade all recently licensed β-lactam-β-lactamase inhibitor combinations, although several stable agents and inhibitor combinations are at various stages in the development pipeline. These potential therapies, along with the epidemiology of producers and current treatment options, are the focus of this review.

摘要

现代医学受到全球抗生素耐药性上升的威胁,尤其是革兰氏阴性菌。金属β-内酰胺酶(MBL)酶是一个特别令人关注的问题,它们在全球范围内日益传播,尤其是在亚洲。许多 MBL 产生者具有多种其他耐药性,使得治疗选择很少。尽管如此,更令人鼓舞的是,在锌缺乏的情况下,MBL 可能对碳青霉烯类药物耐药性的作用不如β-内酰胺酶抑制剂组合有效。由于其独特的结构和功能以及多样性,MBL 对药物开发构成了特殊的挑战。它们逃避了所有最近获得许可的β-内酰胺-β-内酰胺酶抑制剂组合,尽管有几种稳定的试剂和抑制剂组合处于不同的开发阶段。这些潜在的治疗方法,以及产生者的流行病学和当前的治疗选择,是本综述的重点。

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