Metallo-β-Lactamases: Structure, Function, Epidemiology, Treatment Options, and the Development Pipeline
Metallo-β-Lactamases: Structure, Function, Epidemiology, Treatment Options, and the Development Pipeline
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DOI：
10.1128/aac.00397-20
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发表时间：
2020-10-01
影响因子：
4.9
通讯作者：
Hope, William W.
中科院分区：
文献类型：
--
作者：
Boyd, Sara E.;Livermore, David M.;Hope, William W.
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耐药性。金属-β-内酰胺酶 (MBL) 是一个特别令人关注的问题，并且在全世界范围内日益传播，尤其是在亚洲。许多 MBL 生产商还存在多种耐药性，因此几乎没有明显的治疗选择。尽管如此，更令人鼓舞的是，在锌限制下，MBL 在体内的碳青霉烯类抗药性可能不如体外有效。由于其独特的结构和功能以及多样性，MBL 对药物开发提出了特殊的挑战。尽管几种稳定的药物和抑制剂组合处于开发流程的不同阶段，但它们避开了所有最近获得许可的 β-内酰胺-β-内酰胺酶抑制剂组合。这些潜在的疗法以及生产者的流行病学和当前的治疗方案是本次综述的重点。
Modern medicine is threatened by the global rise of antibiotic resistance, especially among Gram-negative bacteria. Metallo-beta-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 in vivo, under zinc limitation, than in vitro. Owing to their unique structure and function and their diversity, MBLs pose a particular challenge for drug development. They evade all recently licensed beta-lactam-beta-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.