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美罗培南-巴坦的微生物学:一种用于耐碳青霉烯类肠杆菌科细菌感染的新型碳青霉烯类β-内酰胺酶抑制剂组合

Microbiology of Meropenem-Vaborbactam: A Novel Carbapenem Beta-Lactamase Inhibitor Combination for Carbapenem-Resistant Enterobacterales Infections.

作者信息

Bhowmick Tanaya, Weinstein Melvin P

机构信息

Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Department of Pathology and Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

出版信息

Infect Dis Ther. 2020 Dec;9(4):757-767. doi: 10.1007/s40121-020-00350-1. Epub 2020 Oct 5.

Abstract

Vaborbactam is a novel boron-based beta-lactamase inhibitor developed to be effective against Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria. This enzyme is a key driver in the global spread of β-lactam resistance among carbapenem-resistant Enterobacterales. Alone, vaborbactam has no antibacterial activity; however, the combination of meropenem-vaborbactam has enhanced activity against gram-negative organisms, particularly Enterobacterales with class A and C carbapenemases. Multiple in vitro studies evaluating isolates from various geographic regions, and over different time periods, have demonstrated the high potency of meropenem-vaborbactam against organisms containing KPC2 and KPC3. However, meropenem-vaborbactam does not have activity against OXA-48 or metallo-beta lactamases. This review covers the in vitro studies of meropenem-vaborbactam performed to date, which evaluated both large cohorts of clinical isolates and engineered isolates, to determine efficacy in various settings, including the presence of porin mutations and efflux pump upregulation.

摘要

瓦博巴坦是一种新型的基于硼的β-内酰胺酶抑制剂,旨在有效对抗产肺炎克雷伯菌碳青霉烯酶(KPC)的细菌。这种酶是耐碳青霉烯类肠杆菌科细菌中β-内酰胺耐药性全球传播的关键驱动因素。单独使用时,瓦博巴坦没有抗菌活性;然而,美罗培南-瓦博巴坦组合对革兰氏阴性菌,特别是具有A类和C类碳青霉烯酶的肠杆菌科细菌,具有增强的活性。多项评估来自不同地理区域和不同时间段分离株的体外研究表明,美罗培南-瓦博巴坦对含有KPC2和KPC3的细菌具有高效力。然而,美罗培南-瓦博巴坦对OXA-48或金属β-内酰胺酶没有活性。本综述涵盖了迄今为止对美罗培南-瓦博巴坦进行的体外研究,这些研究评估了大量临床分离株和工程分离株,以确定其在各种情况下的疗效,包括孔蛋白突变和外排泵上调的情况。

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