title: Comparative efficacies of imipenem-cilastatin and vancomycin in experimental aortic valve endocarditis due to methicillin resistant Staphylococcus aureus.
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.
authors: Department of Internal Medicine, Wayne State University School of Medicine, Detroit Receiving Hospital, Michigan 48201.
authors: P H
authors: PH
authors: Chandrasekar
authors: D P
authors: DP
authors: Levine
authors: S
authors: S
authors: Price
authors: M J
authors: MJ
authors: Rybak
mesh_terms: 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*
chemical_list: D003521:Cyclopropanes; D004338:Drug Combinations; D013845:Thienamycins; D015377:Cilastatin; D014640:Vancomycin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D008712:Methicillin