Open AccessIn Vitro Potentiation of Carbapenems with ME1071, a Novel Metallo-β-Lactamase Inhibitor, against Metallo-β-Lactamase- Producing Pseudomonas aeruginosa Clinical Isolates
Author(s) -
Yoshikazu Ishii,
Maki Eto,
Yoko Mano,
Kazuhiro Tateda,
Keizo Yamaguchi
Publication year - 2010
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01397-09
Subject(s) - doripenem , imipenem , pseudomonas aeruginosa , microbiology and biotechnology , ceftazidime , carbapenem , beta lactamase , beta lactamase inhibitors , biology , pseudomonadaceae , antibacterial agent , antibiotics , bacteria , antibiotic resistance , biochemistry , escherichia coli , genetics , gene
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-producingPseudomonas 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. TheKi value of ME1071 for IMP-1 was 0.4 μM, significantly lower than theKm values of carbapenems for the IMP-1 enzyme. On the other hand, theKi value of ME1071 for VIM-2 was 120 μM, higher than theKm 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 ofP. aeruginosa .