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Antibacterial activity of meropenem against gram-negative bacteria with a permeability defect and against
M D Kitzis1, J F Acar, L Gutmann
1Laboratoire de Microbiologie, Hôpital Saint Joseph, Paris, France.
Abstract:
Meropenem, like imipenem, showed a good affinity for high molecular weight PBPs of Escherichia coli and Pseudomonas aeruginosa and had a better affinity for PBP3 than imipenem. Meropenem, like imipenem, also remained almost fully active against permeability mutants of enterobacteria lacking in confirmed or putative porins. This good permeation of the carbapenems may relate to their zwitterionic character. In-vitro, mutants and clinical isolates of P. aeruginosa, for which the MIC of imipenem was greater than or equal to 4 mg/l, were always more sensitive to meropenem. Methicillin resistant staphylococci were sensitive neither to imipenem nor to meropenem.
Insights
Meropenem exhibits strong binding to bacterial targets and effectively penetrates bacterial cells, showing greater efficacy than imipenem against certain resistant strains. However, neither meropenem nor imipenem are effective against methicillin-resistant staphylococci.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Carbapenem antibiotics like imipenem are crucial for treating severe bacterial infections.
- Understanding the mechanisms of antibiotic resistance, such as altered bacterial cell permeability, is vital.
Purpose of the Study:
- To compare the in vitro activity and target affinity of meropenem and imipenem.
- To investigate the efficacy of meropenem and imipenem against bacterial mutants with altered permeability.
Main Methods:
- Affinity assays for high molecular weight penicillin-binding proteins (PBPs).
- Antimicrobial susceptibility testing (MIC) against wild-type and mutant bacterial strains.
- Evaluation of activity against clinical isolates of Pseudomonas aeruginosa and methicillin-resistant staphylococci.
Main Results:
- Meropenem demonstrated a strong affinity for high molecular weight PBPs in Escherichia coli and Pseudomonas aeruginosa, with a superior affinity for PBP3 compared to imipenem.
- Both carbapenems maintained activity against enterobacterial mutants lacking porins, suggesting good cell penetration attributed to their zwitterionic nature.
- Meropenem showed greater sensitivity than imipenem against imipenem-resistant Pseudomonas aeruginosa isolates (MIC ≥ 4 mg/l).
- Neither antibiotic was effective against methicillin-resistant staphylococci.
Conclusions:
- Meropenem offers advantages over imipenem in terms of PBP binding and activity against specific resistant strains.
- The zwitterionic character of carbapenems facilitates bacterial cell penetration, overcoming certain resistance mechanisms.
- Meropenem and imipenem are not effective against methicillin-resistant staphylococci, necessitating alternative treatment strategies.