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Imipenem: morphological changes and lethal effects on Pseudomonas aeruginosa
N A Carlone1, M Ferrero, A M Cuffini
1Institute of Microbiology, University of Turin, Italy.
Drugs Under Experimental and Clinical Research
|January 1, 1987
Summary
Imipenem, a novel carbapenem antibiotic, exhibits broad-spectrum antibacterial activity and stability against beta-lactamases. It targets penicillin-binding proteins (PBPs), primarily PBP 2, leading to bacterial cell shape changes and lysis.
Area of Science:
- Microbiology
- Pharmacology
- Bacteriology
Background:
- Imipenem is a novel carbapenem antibiotic.
- It demonstrates broad-spectrum activity against Gram-negative and Gram-positive bacteria, including aerobes and anaerobes.
- Imipenem is stable in the presence of beta-lactamases.
Purpose of the Study:
- To investigate the mechanism of action of imipenem.
- To determine the primary bacterial targets of imipenem.
- To elucidate the morphological and ultrastructural changes induced by imipenem in bacteria.
Main Methods:
- Antibacterial activity spectrum analysis.
- Penicillin-binding protein (PBP) affinity studies.
- Microscopic examination of bacterial morphology and ultrastructure (e.g., on Pseudomonas aeruginosa).
- Assessment of bactericidal kinetics.
Main Results:
- Imipenem exhibits high affinity for PBP 2.
- Morphological changes in Pseudomonas aeruginosa include irregular and round cell shapes.
- Later-stage treatment involves PBP 1, leading to cellular lysis.
- Rapid bactericidal effects were observed against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus.
Conclusions:
- Imipenem's primary target is PBP 2, causing initial morphological alterations.
- Involvement of PBP 1 contributes to imipenem's potent bactericidal activity and cell lysis.
- Imipenem represents a significant advancement in broad-spectrum antibiotic therapy.