In Vitro Activity of the New ?-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with ?-Lactams against Mycobacterium abscessus Complex Clinical Isolates.

ABSTRACT: Pulmonary disease due to infection with Mycobacterium abscessus complex (MABC) is notoriously difficult to treat, in large part due to the intrinsic resistance of MABC strains to most antibiotics, including ?-lactams. MABC organisms express a broad-spectrum ?-lactamase that is resistant to traditional ?-lactam-based ?-lactamase inhibitors but inhibited by a newer non-?-lactam-based ?-lactamase inhibitor, avibactam. Consequently, the susceptibility of MABC members to some ?-lactams is increased in the presence of avibactam. Therefore, we hypothesized that two new non-?-lactam-based ?-lactamase inhibitors, relebactam and vaborbactam, would also increase the susceptibility of MABC organisms to ?-lactams. The objective of the present study was to evaluate the in vitro activity of various marketed ?-lactams alone and in combination with either relebactam or vaborbactam against multidrug-resistant MABC clinical isolates. Our data demonstrate that both ?-lactamase inhibitors significantly improved the anti-MABC activity of many carbapenems (including imipenem and meropenem) and cephalosporins (including cefepime, ceftaroline, and cefuroxime). As a meropenem-vaborbactam combination is now marketed and an imipenem-relebactam combination is currently in phase III trials, these fixed combinations may become the ?-lactams of choice for the treatment of MABC infections. Furthermore, given the evolving interest in dual ?-lactam regimens, our results identify select cephalosporins, such as cefuroxime, with superior activity in the presence of a ?-lactamase inhibitor that are deserving of further evaluation in combination with these carbapenem-?-lactamase inhibitor products.

SUBMITTER: Kaushik A 

PROVIDER: S-EPMC6395916 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature