Antimicrobial prophylaxis of experimental endocarditis caused by Staphylococcus epidermidis

Using two different strains of Staphylococcus epidermidis in a rat model of experimental endocarditis, we examined the prophylactic efficacy of cefamandole (200 mg/kg/dose), cefazolin (200 mg/kg/dose), nafcillin (200 mg/kg/dose), and vancomycin (20 mg/kg/dose). In vitro susceptibility testing demonstrated that both test strains were resistant to methicillin and cefazolin and susceptible to cefamandole and vancomycin. A 10(6) cfu inoculum was used for both strains, an inoculum which produced endocardial infections in greater than 90% of rats. Initial doses of each antibiotic were given 45 min to 1 h prior to bacterial challenge and were followed by six additional doses of each antibiotic administered subcutaneously every 6 h. The efficacy rates of cefamandole (84.0%) and cefazolin (70.8%) were exactly the same for rats infected with either S. epidermidis strain. Similar efficacy rates were seen in rats infected with either strain and treated with vancomycin (94.4% and 86.7%). Unlike the other three drugs, the efficacy of nafcillin was quite different in rats challenged with the two strains (62.5% and 38.5%, p = 0.19). It appears that cefamandole and cefazolin may have considerable prophylactic efficacy against certain infecting strains of methicillin-resistant, coagulase-negative staphylococci when relatively large doses of cephalosporins are administered subcutaneously in this animal model.