In vitro and in vivo effects of rifampin on Staphylococcus epidermidis graft infections

Rifampin, bound in high concentrations to prosthetic grafts, has been proposed for the treatment of vascular graft infections. The optimum antibiotic concentration and duration of treatment for infected grafts is not known. This study compared the in vitro and in vivo efficacy of varying concentrations of rifampin against three different strains of slime producing Staphylococcus epidermidis (RP62A, KC2, and KB1) bound to knitted Dacron at high and low concentrations at 10(4) and 10(7) CFU/cm(2) of prosthetic. Time kill experiments were performed at 4, 18, and 42 hr, in which each Dacron bound bacterial strain was exposed in vitro to 4x, 64x, 100x, and 1,000x minimum inhibitory concentration (MIG) of rifampin. In vivo,the Dacron bound laboratory strain RP62A was implanted subcutaneously into the backs of male Swiss-Webster mice and exposed to 4x, 100x, and 1,000x the MIC of rifampin for similar time periods. In addition, systemic vancomycin (10 mg/kg) was assessed for synergy and prevention of rifampin resistance. In vitro,all concentrations of rifampin showed near total killing (<1 log) of all bacterial strains at low initial concentrations (10(4) CFU/cm(2)) but not high (10(7) CFU/cm(2)) to 42 hr. Importantly, resistance was shown to develop in all three strains of S. epidermidis with high initial bacterial biofilm concentrations. In vivo, rifampin concentrations between 4x MIC and 100x MIC achieved a balance between optimal killing and prevention of resistance. Systemic vancomycin slightly improved bacterial clearance but did not alter the development of rifampin resistance at high local concentrations. Caution is advised with the use of antibiotic bonded grafts because resistance may develop, even with the addition of systemic antibiotics.