Endocarditis due to methicillin-resistant Staphylococcus aureus in rabbits: expression of resistance to beta-lactam antibiotics in vivo and in vitro.
Whether a strain of methicillin-resistant Staphylococcus aureus susceptible to cephalothin by the disk-diffusion method was also susceptible to cephalothin in vivo was evaluated in the rabbit model of endocarditis. Rabbits with aortic-valve endocarditis due to methicillin-resistant S. aureus that were treated for four days with cephalothin had the same numbers of organisms in vegetations as did untreated rabbits. Treatment with cephalothin caused emergence of a highly resistant subpopulation in aortic-valve vegetations. Organisms highly resistant to cephalothin were also highly resistant to nafcillin. Thus broth-dilution and disk-diffusion tests may not predict therapeutic failure for cephalothin against strains of methicillin-resistant S. aureus. Because of cross-resistances among beta-lactam drugs, these strains should be considered uniformly resistant to this general class of antimicrobial agents, regardless of results from these tests.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002512:Cephalothin / Q000494:pharmacology / Q000627:therapeutic use; D004697:Endocarditis, Bacterial / Q000188:drug therapy / Q000382:microbiology*; D008712:Methicillin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009254:Nafcillin / Q000494:pharmacology; D010403:Penicillin Resistance; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D009254:Nafcillin; D014640:Vancomycin; D008712:Methicillin; D002512:Cephalothin