A rat model was used to investigate the efficacy of mupirocin in the prevention of vascular prosthetic graft infection due to Staphylococcus epidermidis strains with different susceptibility patterns (methicillin susceptible, methicillin resistant, and with intermediate resistance to vancomycin). The effect of mupirocin-soaked Dacron was compared to that of perioperative intraperitoneal prophylaxis with vancomycin. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses (1 cm 2 ) followed by topical inoculation with 5 ؋ 10 7 CFU of one staphylococcal strain. The study included a control group (no graft contamination), three contaminated groups that did not receive any antibiotic prophylaxis, three contaminated groups that received mupirocin-soaked grafts, three contaminated groups in which perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg of body weight) was administered, and three contaminated groups that received mupirocin-soaked grafts and perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg). The grafts were sterilely removed 7 days after implantation, and the infection was evaluated by using sonication and quantitative agar culture. Data analysis showed the efficacy of mupirocin against all three strains, with growth of the strains in treated rats significantly different than that in the untreated control. In addition, mupirocin was more effective than vancomycin against the strain with intermediate susceptibility to the glycopeptide. Finally, the combination of mupirocin and vancomycin produced complete suppression of the growth of all of the strains.Vascular prosthetic graft infection is a dreaded, serious complication of vascular surgery that frequently results in prolonged hospitalization, organ failure, amputation, and death (2, 3, 23). Staphylococcus epidermidis is among the most common pathogens that cause biomaterial infections (2-4, 18, 23). The centerpiece of prevention is prophylactic systemic antibiotics (4, 17). In addition, in the case of vascular grafts, antimicrobials, bound in high concentrations to prosthetic grafts have been proposed as adjunctive prophylaxis (1,5,6,8,11,12,15). Since the emergence of methicillin-resistant (MR) staphylococci, hglycopeptides have been the only uniformly effective treatment for staphylococcal infections. Vancomycin was introduced in the 1950s, and for almost 3 decades following its introduction, resistance was reported only rarely and appeared to have little clinical significance. Nevertheless, in the 1980s the emergence of vancomycin resistance in coagulase-negative staphylococci, especially S. epidermidis, Staphylococcus hominis, Staphylococcus warneri, Staphylococcus haemolyticus, and Staphylococcus xylous has been described (13,16,20). Mupirocin (pseudomonic acid A), produced by Pseudomonas fluorescens, is a topical antibiotic that is used for the treatment of superficial skin infections due to Staphylococcus aureus and Streptococcus pyogenes and for the erad...