Potency of IMP-10 metallo-beta-lactamase in hydrolysing various antipseudomonal beta-lactams

J Med Microbiol. 2008 Aug;57(Pt 8):974-979. doi: 10.1099/jmm.0.2008/001388-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cephalosporins / metabolism
  • Hydrolysis
  • Microbial Sensitivity Tests
  • Monobactams / metabolism*
  • Monobactams / pharmacology
  • Penicillins / metabolism
  • Sensitivity and Specificity
  • Substrate Specificity
  • beta-Lactamases / metabolism*
  • beta-Lactams / metabolism*
  • beta-Lactams / pharmacology

Substances

  • 7-(1-pentafluorophenoxyacetamido)-3-(2-(5-methyl-1,3,4-thiodiazolyl)thiomethyl)-delta(3)-cephem-4-carboxylic acid
  • Cephalosporins
  • Monobactams
  • Penicillins
  • beta-Lactams
  • beta-lactamase IMP-1
  • beta-Lactamases