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Carbapenems: special properties contributing to their activity.
The American Journal of Medicine
|June 7, 1985
Summary
Imipenem, a potent beta-lactam antibiotic, effectively inhibits many bacteria, including resistant strains. Its stability against beta-lactamases and high affinity for essential bacterial proteins contribute to its broad-spectrum efficacy.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Imipenem is a broad-spectrum beta-lactam antibiotic.
- It exhibits activity against a wide range of bacteria, including Gram-positive and Gram-negative pathogens.
- Understanding its mechanism of action and resistance patterns is crucial for effective clinical use.
Purpose of the Study:
- To evaluate the in vitro activity of imipenem against various bacterial isolates.
- To investigate the mechanisms underlying imipenem's efficacy and potential resistance.
- To assess the synergistic effects of imipenem with other antibiotics.
Main Methods:
- In vitro susceptibility testing against clinical isolates of staphylococci, Enterobacteriaceae, streptococci, and Pseudomonas species.
- Determination of minimal inhibitory concentrations (MICs).
- Assessment of beta-lactamase stability and interaction with bacterial penicillin-binding proteins (PBPs).
Main Results:
- Imipenem inhibited most staphylococci, Enterobacteriaceae, and streptococci at low concentrations (≤1 µg/ml), excluding enterococci.
- Resistance was infrequently observed in methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens.
- Pseudomonas maltophilia demonstrated intrinsic resistance.
- Many cephalosporin-resistant strains were susceptible to imipenem, albeit with higher MICs.
- Imipenem exhibited high stability against plasmid and chromosomal beta-lactamases, acting as a suicide inhibitor.
- Synergistic activity was observed with aminoglycosides against certain bacteria, notably Streptococcus faecalis, S. aureus, and P. aeruginosa.
Conclusions:
- Imipenem possesses excellent broad-spectrum antibacterial activity due to its lack of a permeability barrier, high affinity for PBPs, and significant beta-lactamase stability.
- It remains effective against many organisms resistant to other beta-lactams and aminoglycosides.
- Imipenem's stability and unique mechanism make it a valuable therapeutic option, though resistance can emerge in specific pathogens.