In Vivo Efficacy of an Antibiotic Wound Gel in a Sheep Model of Bone Trauma and Biofilm-Related Infection.

Abstract

Traumatic extremity injuries suffer a high probability of infection and often amputation due to contamination and delays in treatment. Military service members are predisposed to injury while engaged in conflict, yet current military adherence to antibiotic administration protocols following traumatic injury is lacking. Moreover, systemic antibiotic prophylaxis might not effectively eradicate biofilm throughout the wound site. Previously, an antibiotic wound gel was created to address current limitations of prophylactic antibiotic treatment in austere environments, particularly the battlefield, by offering a simple solution to control the release of tobramycin over a one-week period. We hypothesized that tobramycin eluted from the gel would effectively manage biofilm-related infection when tested in a large animal model of traumatic long-bone injury. Sheep were either treated with tobramycin-loaded gel or gel alone, and the reduction in bioburden was determined by quantifying tissue and inoculation substrates after a one-week period. Results indicated the wound gel was effective at managing biofilm in this model, with no detectable growth observed in tissues collected from treated animals. Further, the antibiotic-loaded wound gel significantly reduced the severity of the inflammatory response in the surrounding tissue. Biofilm presence was confirmed in scanning electron and light microscopy images of tissues treated with gel alone. Additionally, reactive bone growth, a characteristic of biofilm infection, was consistently observed in all untreated animals but appeared effectively managed in those treated with the antibiotic wound gel. Localized delivery of a broad-spectrum antibiotic from a controlled-release gel can improve adherence to antibiotic administration guidelines and has a greater potential to stabilize biofilm-contaminated wound sites quickly after injury while also mitigating a severe inflammatory response.