In Vitro Potentiation of Carbapenems with ME1071, a Novel Metallo-β-Lactamase Inhibitor, against Metallo-β-Lactamase- Producing Pseudomonas aeruginosa Clinical Isolates▿

摘要

ME1071, a maleic acid derivative, is a novel specific inhibitor for metallo-β-lactamases (MBL). In this study, the potentiation of ME1071 in combination with several β-lactams was evaluated using MBL-producing Pseudomonas aeruginosa isolates. The rates of susceptibility of MBL producers to carbapenems (imipenem, biapenem, and doripenem) and ceftazidime were increased by 8 to 27% in the presence of 32 μg/ml of ME1071. The corresponding resistance rates were decreased by 13 to 46%, respectively. On the other hand, ME1071 showed weaker or no potentiation with non-MBL producers. The Ki value of ME1071 for IMP-1 was 0.4 μM, significantly lower than the Km values of carbapenems for the IMP-1 enzyme. On the other hand, the Ki value of ME1071 for VIM-2 was 120 μM, higher than the Km values of carbapenems for the VIM-2 enzyme. Results of this study indicate that ME1071 can potentiate the activity of ceftazidime and carbapenems against MBL-producing strains of P. aeruginosa.