title: Local application of vancomycin for prophylaxis of graft infection: release of vancomycin from antibiotic-bonded Dacron grafts, toxicity in endothelial cell culture, and efficacy against graft infection in an animal model.
abstract: Methicillin-resistant strains of Staphylococcus epidermidis cause an increasing number of prosthetic infections. This prompted us to test the uptake of vancomycin in various graft materials in vitro, its influence on graft healing, and its efficacy against graft infection in pigs. Incubation of six different Dacron graft materials in a vancomycin solution (20 gm/L) was performed. Grafts were then placed in plasma, and samples were taken over 72 hours to determine vancomycin levels. Release of vancomycin ranged from 775 micrograms/cm2 to 3691 micrograms/cm2 after 1 hour of incubation. Gelatin-covered grafts increased release of vancomycin fourfold when incubation time was extended to 24 hours: uncovered grafts or the collagen-covered graft did not. Graft healing was not complicated when a vancomycin-bonded, gelatin-impregnated Dacron graft was implanted to replace the common femoral artery in pigs. Four weeks after implantation, histologic examination revealed normal development of neointima and perigraft scar tissue in the vancomycin-treated (n = 4) and untreated (n = 5) grafts. To test the efficacy of local vancomycin against graft infection, grafts were implanted in the groin of pigs and contaminated with 2 x 10(7) colony-forming units of Staphylococcus aureus. Four weeks after implantation, all grafts were infected in the untreated group (n = 6), with abscess, nonincorporated graft, and detection of S. aureus from the graft. In the treatment group (n = 6) vancomycin was added to the contaminated grafts. As a carrier for the vancomycin, we used a resorbable gelatin-glycerol foam. All grafts healed without infection. The difference between the treated and untreated groups is statistically significant (p < 0.05). We conclude that it may be effective to prevent graft infection with local application of vancomycin if an in situ replacement of infected graft (infected by gram-positive bacteria) is necessary or if there is a high risk of infection by methicillin-resistant- staphylococci.
authors.affiliation: Department of Surgery, University of Luebeck, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Muhl
authors.forename: S
authors.initials: S
authors.lastname: Gatermann
authors.forename: H
authors.initials: H
authors.lastname: Iven
authors.forename: A
authors.initials: A
authors.lastname: Dendorfer
authors.forename: H P
authors.initials: HP
authors.lastname: Bruch
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis / Q000379:methods*; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects*; D005263:Femoral Artery / Q000601:surgery; D011093:Polyethylene Terephthalates; D011474:Prosthesis Design; D016459:Prosthesis-Related Infections / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013212:Staphylococcus epidermidis; D013552:Swine; D017334:Teicoplanin / Q000494:pharmacology; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D011093:Polyethylene Terephthalates; D017334:Teicoplanin; D014640:Vancomycin