The efficacy of ticarcillin-clavulanic acid was compared with the efficacies of standard antistaphylococcal agents (flucloxacillin, oxacillin, nafcillin, and vancomycin) and ticarcillin in an experimental model of Staphylococcus aureus endocarditis. Therapy was either initiated soon (8 h) after infection, when numbers of bacteria in aortic valve vegetations were relatively low (approximately 6 to 8 log1o CFU/g), or delayed until 24 h after infection, when the vegetations usually contained >9 loglo CFU/g. Doses of the antibiotic were selected to produce peak concentrations in rat serum similar to those achievable in humans after administration of parenteral therapeutic doses. Ticarcillin-clavulanic acid was more effective overall than ticarcillin alone against endocarditis caused by ,I-lactamase-producing strains of S. aureus, illustrating the P-lactamase-inhibitory activity of clavulanic acid in vivo. Ticarcillin-clavulanic acid was as effective as the standard antistaphylococcal ,-lactam agents flucloxacillin, oxacillin, and nafcillin in these infections, whereas vancomycin was generally less active. These results illustrate the clinical potential of ticarcillin-clavulanic acid in the prophylaxis or therapy of severe staphylococcal infections.Staphylococcus aureus remains a major pathogen, and 80% to greater than 90% of clinical isolates of S. aureus are 3-lactamase producers (10, 17). Clavulanic acid is a potent inhibitor of a wide range of bacterial 3-lactamases, including those produced by S. aureus (22). The combination of ticarcillin and clavulanic acid has been shown to extend the spectrum of ticarcillin to include P-lactamase-producing strains both in vitro (29) and in vivo (2, 21, 29), and successful treatment of clinical staphylococcal infections with ticarcillin-clavulanic acid has been reported (9, 15).Experimental Staphylococcus endocarditis represents one of the more severe of the available animal models of staphylococcal infections. It is considered to be a discriminative model closely resembling the human infection in pathology and mortality (10,25) and is a stringent test of antibiotic efficacy, especially when therapy is delayed until the endocarditis is particularly well established.The combination of clavulanic acid with amoxicillin has been shown to be effective in rats against early endocarditis in which the vegetations contained approximately 6 to 8 log1o CFU of S. aureus per g (3, 5) and against late S. aureus endocarditis in which bacterial counts were 9 to 10 log1o CFU/g (5). The activity of a combination of clavulanic acid with ticarcillin against S. aureus endocarditis in rabbits has been reported elsewhere (7,24). Accordingly, the efficacy of ticarcillin-clavulanic acid in rats against early and late endocarditis caused by four ,-lactamase-producing, methicillin-susceptible strains of S. aureus has been assessed. The activity of the combination was compared with that of ticarcillin alone and with the activities of agents commonly employed in the treatment of staphylococcal infections...

The efficacy of amoxycillin/clavulanic acid was compared with that of flucloxacillin, vancomycin and amoxycillin in an experimental model of Staphylococcus aureus endocarditis. Doses of the antibiotics were selected to produce peak concentrations in rat serum similar to those achievable in man after administration of parenteral therapeutic doses. Amoxycillin clavulanic acid was more effective than amoxycillin alone against endocarditis caused by beta-lactamase producing strains of Staph. aureus, illustrating the beta-lactamase inhibitory activity of clavulanic acid in vivo. Amoxycillin/clavulanic acid was as effective as flucloxacillin in these infections whereas vancomycin was generally less active. These results illustrate the clinical potential of amoxycillin/clavulanic acid in the prophylaxis, or in the therapy of severe staphylococcal infections.