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Published on: February 1, 2018
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.
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.
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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