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 a ntibiotic 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) boun d 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 i n vitro to 4x, 64x, 100x, and 1,000x minimum inhibitory concentration (MIG) of rifampin. In vivo,the Dacron bound laboratory strain RP62A wa s implanted subcutaneously into the backs of male Swiss-Webster mice a nd exposed to 4x, 100x, and 1,000x the MIC of rifampin for similar tim e periods. In addition, systemic vancomycin (10 mg/kg) was assessed fo r synergy and prevention of rifampin resistance. In vitro,all concentr ations 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 devel op in all three strains of S. epidermidis with high initial bacterial biofilm concentrations. In vivo, rifampin concentrations between 4x MI C and 100x MIC achieved a balance between optimal killing and preventi on of resistance. Systemic vancomycin slightly improved bacterial clea rance but did not alter the development of rifampin resistance at high local concentrations. Caution is advised with the use of antibiotic b onded grafts because resistance may develop, even with the addition of systemic antibiotics.