In Vitro Activity of the Ultra-Broad-Spectrum Beta-lactamase Inhibitor QPX7728 in Combination with Meropenem against Clinical Isolates of Carbapenem-Resistant Acinetobacter baumannii.

In Vitro Activity of the Ultra-Broad-Spectrum Beta-lactamase Inhibitor QPX7728 in Combination with Meropenem against Clinical Isolates of Carbapenem-Resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2020 Aug 31;: Authors: Nelson K, Rubio-Aparicio D, Tsivkovski R, Sun D, Totrov M, Dudley M, Lomovskaya O Abstract QPX7728 is a recently discovered ultra-broad-spectrum beta-lactamase inhibitor (BLI) with potent inhibition of key serine and metallo beta-lactamases. QPX7728 enhances the potency of many beta-lactams, including carbapenems, in beta-lactamase producing gram-negative bacteria, including Acinetobacter spp. The potency of meropenem alone and in combination with QPX7728 (1-16 μg/ml) was tested against 275 clinical isolates of Acinetobacter baumannii (CRAB) collected worldwide that were highly resistant to carbapenems (MIC50/MIC90 for meropenem 64/>64 μg/ml). Addition of QPX7728 resulted in a marked concentration-dependent increase in meropenem potency with MIC90 of meropenem alone decreasing from >64 μg/ml to 8- and 4 μg/ml when tested with a fixed concentration of QPX7728 at 4 and 8 μg/ml, respectively. In order to identify the mechanisms that modulate meropenem-QPX7728 MIC, whole genome sequence was determined for 135 isolates with a wide distribution of meropenem-QPX7728 MIC. This panel of strains included 116 strains producing OXA-carbapenemases (71 OXA-23, 16 OXA-72, 16 OXA-24, 9 OXA-58, 4 OXA-239), 5...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research