title: Beta-lactamase stability and inhibitory activity of meropenem combined with a potent antibacterial activity.
abstract: The affinity of meropenem for various known types of beta-lactamases and its stability to them were tested in comparison with other beta-lactams, including imipenem. Meropenem exhibited a marked stability to all beta-lactamases tested and was only hydrolyzed by Xanthomonas maltophilia beta-lactamase, as were other beta-lactams. This was responsible for the potent antibacterial activities of meropenem against beta-lactamase-producing strains. Meropenem and imipenem had almost the same, relatively high affinity for beta-lactamases; however, they had a lower affinity than clavulanic acid for penicillin beta-lactamases and cefoxitin for cephalosporin beta-lactamases. Meropenem also had higher beta-lactamase inhibitory activity than imipenem. Meropenem inhibited type III (TEM-1), Ia Citrobacter freundii and Ic Proteus vulgaris beta-lactamases in a progressive manner. Meropenem was thought to be a potent inhibitor of various beta-lactamase because of its ability to form stable enzyme-meropenem acyl-complexes. Meropenem generally exhibited a lower induction potential than imipenem against five clinical isolates of C. freundii, Enterobacter cloacae and Pseudomonas aeruginosa, but its induction potential was higher than that of ceftazidime. Meropenem induced beta-lactamases at concentrations above the MIC.
authors: Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
authors: H
authors: H
authors: Nouda
authors: E T
authors: ET
authors: Harabe
authors: Y
authors: Y
authors: Sumita
authors: T
authors: T
authors: Okuda
authors: M
authors: M
authors: Fukasawa
mesh_terms: D001419:Bacteria / Q000201:enzymology*; D002442:Ceftazidime / Q000494:pharmacology; D004790:Enzyme Induction; D004795:Enzyme Stability; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D013845:Thienamycins / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis
chemical_list: D013845:Thienamycins; D065093:beta-Lactamase Inhibitors; D015378:Imipenem; D002442:Ceftazidime; D001618:beta-Lactamases; D000077731:Meropenem