Topical Delivery of Ultrahigh Concentrations of Gentamicin Is Highly Effective in Reducing Bacterial Levels in Infected Porcine Full-Thickness Wounds

Background: Injury to the skin can predispose individuals to invasive infection. The standard of care for infected wounds is treatment with intravenous antibiotics. However, antibiotics delivered intravenously may have poor tissue penetration and be dose limited by systemic side effects. Topical delivery of antibiotics reduces systemic complications and delivers increased drug concentrations directly to the wound. Methods: Porcine full-thickness wounds infected with Staphylococcus aureus were treated with ultrahigh concentrations (over 1000 times the minimum inhibitory concentration) of gentamicin using an incubator-like wound healing platform. The aim of the present study was to evaluate clearance of infection and reduction in inflammation following treatment. Gentamicin cytotoxicity was evaluated by in vitro assays. Results: Application of 2000 mu g/ml gentamicin decreased bacterial counts in wound tissue from 7.2 +/- 0.3 log colony-forming units/g to 2.6 +/- 0.6 log colony-forming units/g in 6 hours, with no reduction observed in saline controls (p < 0.005). Bacterial counts in wound fluid decreased from 5.7 +/- 0.9 log colony-forming units/ml to 0.0 +/- 0 log colony-forming units/ml in 1 hour, with no reduction observed in saline controls (p < 0.005). Levels of interleukin-1 beta were significantly reduced in gentamicin-treated wounds compared with saline controls (p < 0.005). In vitro, keratinocyte migration and proliferation were reduced at gentamicin concentrations between 100 and 1000 mu g/ml. Conclusions: Topical delivery of ultrahigh concentrations of gentamicin rapidly decontaminates acutely infected wounds and maintains safe systemic levels. Treatment of infected wounds using the proposed methodology protects the wound and establishes a favorable baseline for subsequent treatment.