Comprehensive evaluation of fibrin glue as a local drug-delivery system—efficacy and safety of sustained release of vancomycin by fibrin glue against local methicillin-resistant Staphylococcus aureus infection

Abstract

Infection of prosthetic grafts, especially with methicillin-resistant Staphylococcus aureus (MRSA), often becomes critical. Although topical administration of antibiotics has been applied empirically, no comprehensive data are available showing long-lasting effects and safety of local antibiotic usage. By means of animal experiments we assessed fibrin glue (FG) as a slow-release vehicle for vancomycin (VCM) against local MRSA infection. Preliminary in-vitro experiments were performed to confirm that the FG–VCM mixture maintained viscosity as a sealant and led to slow-release of VCM. We next created a subcutaneous pocket in a rodent back and implanted a 1 cm ² woven graft with 1 ml FG alone, or with serial concentrations of VCM (0–120 mg/ml. n = 3 for each group). MRSA of 1 × 10⁷ colony-forming units (CFU) was injected into the pocket after wound closure. The graft was explanted 7 days later and was submitted for culture (“Culture–graft”). Blood samples were obtained for regular blood work, serum VCM concentration measurements, and blood culture (“Culture–blood”). The pocket tissue was also submitted for measurement of local VCM concentration. There was a remarkable infectious response in the group without vancomycin; however, no other groups developed any sign of infection. “Culture–graft” resulted in MRSA growth for V0 only. “Culture–blood” was negative in all groups, and only minimal serum concentrations of vancomycin were detected. One-dose topical administration of VCM via FG was effective against localized MRSA graft infection without systemic VCM administration. Topical administration of antibiotics may help treat difficult graft infections and reduce systemic use of potent antibiotics.