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

Wei-Hua Zhao1, Zhi-Qing Hu1, Tadakatsu Shimamura1

  • 1Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo 142-8555, Japan.

Insights

Metallo-beta-lactamases (MBLs) like IMP-10 reduce the effectiveness of many antipseudomonal beta-lactams. This study reveals which antibiotics remain potent against Pseudomonas aeruginosa with IMP-10, aiding clinical selection.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • The emergence of metallo-beta-lactamases (MBLs), particularly IMP-type, poses a significant threat to treating Pseudomonas aeruginosa infections.
  • MBLs exhibit broad substrate specificity and resistance to available inhibitors, limiting the utility of beta-lactam antibiotics.

Purpose of the Study:

  • To assess the hydrolytic activity of IMP-10 MBL against clinically relevant antipseudomonal beta-lactams.
  • To determine the susceptibility profile of various beta-lactam antibiotics to IMP-10 hydrolysis.

Main Methods:

  • Crude IMP-10 MBL was isolated from clinical Pseudomonas aeruginosa strains carrying the bla(IMP-10) gene.
  • Minimum Inhibitory Concentrations (MICs) of 14 antipseudomonal beta-lactams were compared against a susceptible P. aeruginosa strain, with and without the presence of IMP-10 MBL.

Main Results:

  • Carbapenems (imipenem, meropenem, panipenem) and extended-spectrum cephems (ceftazidime, cefoperazone, cefsulodin, cefepime) were found to be sensitive to IMP-10 MBL hydrolysis.
  • Fourth-generation cephems (cefpirome), extended-spectrum penicillins (carbenicillin, ticarcillin, piperacillin, mezlocillin), and monobactams (aztreonam, carumonam) demonstrated relative resistance to IMP-10 MBL.

Conclusions:

  • The study provides a crucial sensitivity profile of antipseudomonal beta-lactams against IMP-10 MBL.
  • This information serves as a valuable reference for healthcare professionals in selecting appropriate antibiotics for Pseudomonas aeruginosa infections in the presence of IMP-10.
  • Understanding these resistance mechanisms is vital for effective antimicrobial stewardship.

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