Efficacy of polycationic peptides in preventing vascular graft infection due to Staphylococcus epidermidis

J Antimicrob Chemother. 2000 Nov;46(5):751-6. doi: 10.1093/jac/46.5.751.

Abstract

A rat model was used to investigate the efficacy of two polycationic peptides, ranalexin and buforin II, in the prevention of vascular prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with intermediate resistance to glycopeptides. The in vitro activity of the peptides was compared with those of vancomycin and teicoplanin by MIC determination and time-kill study. Moreover, the efficacy of collagen-sealed peptide-soaked Dacron was evaluated in a rat model of graft infection. Graft infections were established in the dorsal subcutaneous tissue of 120 adult male Wistar rats. The in vivo study included a control group, one contaminated group that did not receive any antibiotic prophylaxis and four contaminated groups that received an antibiotic-soaked graft. Experiments demonstrated that the activities of buforin II and ranalexin were greater than those of vancomycin and teicoplanin. Particularly, rats with buforin II-coated Dacron grafts showed no evidence of staphylococcal infection while, for the rats with ranalexin-, vancomycin- and teicoplanin-coated Dacron grafts, the quantitative graft cultures demonstrated bacterial growth (1.9 x 10(2) +/- 0.6 x 10(2) cfu/mL, 6. 2 x 103 +/- 1.9 x 10(3) cfu/mL and 5.1 x 10(4) +/- 4.8 x 10(3) cfu/mL, respectively). The study demonstrated that the use of peptide-soaked Dacron graft can result in significant bacterial growth inhibition and indicates that these compounds may be potentially useful in prosthetic surgery.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Blood Vessel Prosthesis / microbiology*
  • Drug Evaluation
  • Male
  • Models, Animal*
  • Peptides, Cyclic / pharmacology
  • Peptides, Cyclic / therapeutic use*
  • Proteins / pharmacology
  • Proteins / therapeutic use*
  • Rats
  • Rats, Wistar
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / immunology
  • Staphylococcus epidermidis* / drug effects
  • Staphylococcus epidermidis* / immunology

Substances

  • Anti-Bacterial Agents
  • Peptides, Cyclic
  • Proteins
  • buforin II
  • ranalexin