Endocarditis Due to Methicillin-Resistant Staphylococcus aureus in Rabbits: Expression of Resistance to -Lactam Antibiotics in Vivo and in Vitro

Abstract

Whether a strain of methicillin-resistant S. aureus susceptible to cephalothin by the disc 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 4 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 disc 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.