The lipopeptides Pal–Lys–Lys–NH2 and Pal–Lys–Lys soaking alone and in combination with intraperitoneal vancomycin prevent vascular graft biofilm in a subcutaneous rat pouch model of staphylococcal infection

Staphylococcal infections are often associated with the use of implantable medical devices. Such infections are difficult to treat because of biofilm resistance to antibiotics and are common causes of morbidity and mortality. 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 × 107 colony-forming units of bacterial strains. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and five contaminated groups that received intraperitoneal vancomycin, Pal–Lys–Lys–NH2 and Pal–Lys–Lys-soacked graft, and vancomycin plus Pal–Lys–Lys–NH2 or Pal–Lys–Lys-soacked graft, respectively. The infection was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro antibiotic susceptibility assay for Staphylococcus aureus biofilms was performed to elucidate the same activity. When tested alone, vancomycin and lipopeptides showed comparable efficacies. All combinations showed efficacies significantly higher than that of each single compound. Vancomycin combined to Pal–Lys–Lys–NH2 exerted the strongest anti-staphylococcal efficacies. The in vitro studies showed, that MIC and MBC values for vancomycin were lower in presence of lipopeptides. They reduce the bacterial load and to enhance the effect of vancomycin in the prevention of vascular graft staphylococcal infections.