Daptomycin and Rifampin Alone and in Combination Prevent Vascular Graft Biofilm Formation and Emergence of Antibiotic Resistance in a Subcutaneous Rat Pouch Model of Staphylococcal Infection

Abstract

Objective To investigate the efficacy of daptomycin and rifampin either alone or in combination in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Design Prospective, randomised, controlled animal study. Materials Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 × 10 7 colony forming units of Staphylococcus aureus, strain Smith diffuse. Methods The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and three contaminated groups that received intra-peritoneal daptomycin, rifampin-soaked graft and daptomycin plus rifampin-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro antibiotic susceptibility assay for S. aureus biofilms was performed to elucidate the same activity. Results When tested alone, daptomycin and rifampin showed good efficacies. Their combination showed efficacies significantly higher than that of each single compound. The in vitro studies showed that Minimum Inhibitory Concentration and Minimum Bactericidal Concentration values for daptomycin were lower in presence of rifampin. Daptomycin prevented the emergence of rifampin resistance. Conclusion Daptomycin is an important candidate for prevention of staphylococcal biofilm-related infection and rifampin could serve as an interesting anti-staphylococcal antibiotic enhancer.