title: In vitro potentiation of carbapenems with ME1071, a novel metallo-beta-lactamase inhibitor, against metallo-beta-lactamase- producing Pseudomonas aeruginosa clinical isolates.
abstract: ME1071, a maleic acid derivative, is a novel specific inhibitor for metallo-beta-lactamases (MBL). In this study, the potentiation of ME1071 in combination with several beta-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 microg/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 K(i) value of ME1071 for IMP-1 was 0.4 microM, significantly lower than the K(m) values of carbapenems for the IMP-1 enzyme. On the other hand, the K(i) value of ME1071 for VIM-2 was 120 microM, higher than the K(m) 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.
authors.affiliation: Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143 8540, Japan. yishii@med.toho-u.ac.jp.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishii
authors.forename: Maki
authors.initials: M
authors.lastname: Eto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mano
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D015780:Carbapenems / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D015780:Carbapenems; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases