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Comparative efficacies of imipenem-cilastatin and vancomycin in experimental aortic valve endocarditis due to
P H Chandrasekar1, D P Levine, S Price
1Department of Internal Medicine, Wayne State University School of Medicine, Detroit Receiving Hospital, Michigan 48201.
Abstract:
Activities of imipenem and vancomycin against methicillin resistant Staphylococcus aureus (MRSA) were compared in vitro and in a rabbit model of aortic valve endocarditis. Against 25 MRSA clinical isolates, imipenem was bacteriostatic (MIC90/MBC90, mg/l 8/32) in vitro while vancomycin was bactericidal (MIC90/MBC90, mg/l 2/4). Rabbit endocarditis was produced with a MRSA isolate against which both drugs were bactericidal. Imipenem-cilastatin had better efficacy than vancomycin by the following criteria, the number of survivors (9/13 vs 7/13), clearance of bacteraemia (9/9 vs 3/7; P = 0.019), sterility of cardiac vegetations (9/9 vs 1/7; P = 0.001) and sterility of distant organs (8/9 vs 2/7; P = 0.035). Thus, imipenem-cilastatin may be a potentially useful alternative agent to vancomycin in the therapy of MRSA endocarditis in the occasional situations when the drug demonstrates in-vitro bactericidal activity against the pathogen. Efficacy against MRSA strains with higher MBCs remains to be proved.
Insights
Imipenem-cilastatin showed greater efficacy than vancomycin in treating methicillin-resistant Staphylococcus aureus (MRSA) endocarditis in rabbits. This suggests imipenem-cilastatin may be a viable alternative for MRSA endocarditis when bactericidal activity is observed.
Area of Science:
- Infectious Diseases
- Pharmacology
- Microbiology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of infectious endocarditis.
- Vancomycin is a standard treatment, but concerns exist regarding its efficacy and emerging resistance.
- Alternative therapeutic options for MRSA endocarditis are needed.
Purpose of the Study:
- To compare the in vitro and in vivo efficacy of imipenem-cilastatin and vancomycin against MRSA.
- To evaluate the effectiveness of imipenem-cilastatin as a potential alternative to vancomycin for MRSA endocarditis.
Main Methods:
- In vitro susceptibility testing (MIC/MBC) of imipenem and vancomycin against 25 MRSA clinical isolates.
- Establishment of a rabbit model of aortic valve endocarditis using an MRSA isolate.
- Comparison of treatment outcomes, including survival, bacterial clearance, and organ sterility, between imipenem-cilastatin and vancomycin groups.
Main Results:
- In vitro, imipenem was bacteriostatic (MIC90/MBC90: 8/32 mg/L) while vancomycin was bactericidal (MIC90/MBC90: 2/4 mg/L).
- In the rabbit endocarditis model, imipenem-cilastatin demonstrated superior efficacy compared to vancomycin.
- Key indicators of improved efficacy for imipenem-cilastatin included higher survival rates (9/13 vs 7/13), more effective clearance of bacteremia (9/9 vs 3/7), and greater sterility of cardiac vegetations (9/9 vs 1/7) and distant organs (8/9 vs 2/7).
Conclusions:
- Imipenem-cilastatin exhibited enhanced efficacy over vancomycin in a rabbit model of MRSA endocarditis.
- Imipenem-cilastatin may serve as a valuable alternative for MRSA endocarditis, particularly when in vitro bactericidal activity is demonstrated.
- Further studies are warranted to confirm efficacy against MRSA strains with higher minimum bactericidal concentrations (MBCs).