Discovery of a Novel Metallo- ß-Lactamase Inhibitor, which can Potentiate Meropenem Activity against Carbapenem-Resistant Enterobacteriaceae.

Discovery of a Novel Metallo-ß-Lactamase Inhibitor, which can Potentiate Meropenem Activity against Carbapenem-Resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2018 Mar 12;: Authors: Everett M, Sprynski N, Coelho A, Castandet J, Bayet M, Bougnon J, Lozano C, Davies DT, Leiris S, Zalacain M, Morrissey I, Magnet S, Holden K, Warn P, De Luca F, Docquier JD, Lemonnier M Abstract Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent and have become a major worldwide threat to human health. Carbapenem resistance is driven primarily by the acquisition of β-lactamase enzymes which are able to degrade carbapenem antibiotics (hence termed carbapenemases) and can result in high levels of resistance and treatment failure. Clinically relevant carbapenemases include both serine-β-lactamases (SBLs, e.g. KPC-2 and OXA-48) and metallo-β-lactamases (MBLs), such as NDM-1. MBL-producing strains are endemic within the community in many Asian countries, have successfully spread worldwide, and account for many significant CRE outbreaks. Recently approved combinations of β-lactam antibiotics with β-lactamase inhibitors are only active against SBL-producing pathogens. Therefore, new drugs that specifically target MBLs and which restore carbapenem efficacy against MBL-producing CRE pathogens are urgently needed. Here, we report the discovery of a novel MBL inhibitor, ANT431, that can potentiate the activ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research