title: Potency of IMP-10 metallo-beta-lactamase in hydrolysing various antipseudomonal beta-lactams.
abstract: Limited beta-lactams show antipseudomonal activity. The rapid spread of IMP-type metallo-beta-lactamases (MBLs), which have a broad spectrum of substrates and a poor susceptibility to clinically available inhibitors, further restricts beta-lactam use. In the present study, we evaluated the potency of IMP-10 MBL in hydrolysing antipseudomonal beta-lactams currently available in the clinic. Crude IMP-10 MBL was prepared from two clinical isolates of Pseudomonas aeruginosa harbouring the bla(IMP-10) gene. The sensitivity of beta-lactams to hydrolysis by IMP-10 MBL was determined by comparing the MICs of 14 antipseudomonal beta-lactams against a susceptible strain of P. aeruginosa in the presence and absence of IMP-10 MBL. Carbapenems (imipenem, meropenem and panipenem) and extended-spectrum cephems (ceftazidime, cefoperazone, cefsulodin and cefepime) were sensitive to the hydrolysing activity of IMP-10 MBL. By comparison, the fourth-generation cephem (cefpirome), the extended-spectrum penicillins (carbenicillin, ticarcillin, piperacillin and mezlocillin) and monobactams (aztreonam and carumonam) were relatively resistant to IMP-10 MBL. The sensitivity profile of antipseudomonal beta-lactams to IMP-10 MBL generated in the present study provides a valuable reference for antibiotic selection by medical professionals.
authors.affiliation: Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo 142-8555, Japan.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Zhao
authors.affiliation: Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo 142-8555, Japan.
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Hu
authors.affiliation: Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo 142-8555, Japan.
authors.forename: Tadakatsu
authors.initials: T
authors.lastname: Shimamura
mesh_terms: D002511:Cephalosporins / Q000378:metabolism; D006868:Hydrolysis; D008826:Microbial Sensitivity Tests; D008997:Monobactams / Q000378:metabolism* / Q000494:pharmacology; D010406:Penicillins / Q000378:metabolism; D012680:Sensitivity and Specificity; D013379:Substrate Specificity; D001618:beta-Lactamases / Q000378:metabolism*; D047090:beta-Lactams / Q000378:metabolism* / Q000494:pharmacology; D005464:Fluorobenzenes; D005466:Fluorocarbons
chemical_list: D002511:Cephalosporins; D008997:Monobactams; D010406:Penicillins; D001618:beta-Lactamases; D047090:beta-Lactams; C483605:7-(1-pentafluorophenoxyacetamido)-3-(2-(5-methyl-1,3,4-thiodiazolyl)thiomethyl)-delta(3)-cephem-4-carboxylic acid; D005464:Fluorobenzenes; D005466:Fluorocarbons; C409201:beta-lactamase IMP-1