Comparative efficacies of imipenem-cilastatin and vancomycin in experimental aortic valve endocarditis due to methicillin resistant Staphylococcus aureus.
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.
Chandrasekar
P H
PH
Department of Internal Medicine, Wayne State University School of Medicine, Detroit Receiving Hospital, Michigan 48201.
Levine
D P
DP
Price
S
S
Rybak
M J
MJ
D000818:Animals; D001021:Aortic Valve; D015377:Cilastatin; D000077728:Cilastatin, Imipenem Drug Combination; D003521:Cyclopropanes / Q000494:pharmacology / Q000627:therapeutic use; D004338:Drug Combinations / Q000494:pharmacology / Q000627:therapeutic use; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D006349:Heart Valve Diseases / Q000188:drug therapy / Q000382:microbiology; D015378:Imipenem; D008712:Methicillin / Q000494:pharmacology; D010403:Penicillin Resistance; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D013845:Thienamycins / Q000494:pharmacology / Q000627:therapeutic use; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use*
D003521:Cyclopropanes; D004338:Drug Combinations; D013845:Thienamycins; D015377:Cilastatin; D014640:Vancomycin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D008712:Methicillin