Does Prophylactic Local Tobramycin Injection Lower Open Fracture Infection Rates?

Background: The proposed study will address the CTA focus area of Translation of early research findings under the category of fracture related infection. Fracture related infections (FRI) result in significant patient morbidity with delayed fracture healing, diminished quality of life, increased mortality, and represent a substantial financial burden on the health care system. Open fractures sustained from traumatic orthopaedic injuries are particularly at a higher risk for FRI and nonunion due to damage of the soft tissue envelope and impaired bone vascularity compromising bone healing and diminishing host defenses against bacteria. Hypothesis/Objective: The present study will test the hypothesis that administering a validated local dose of tobramycin injection in combination with systemic perioperative intravenous (IV) antibiotic prophylaxis will reduce the rate of deep surgical site infection (SSI) 1 year after open fracture fixation surgery. This study will also determine bacterial speciation and antibiotic sensitivity among study patients who develop deep SSI as well as nonunion status among all participants. Specific Aims: Aim 1: Determine if a validated local dose of tobramycin (2 mg/mL) injection in combination with systemic perioperative IV antibiotic prophylaxis (weight based cefazolin or clindamycin if penicillin-allergic) will reduce the rate of deep SSI 1 year after open fracture fixation surgery. Aim 2: Determine bacterial speciation and antibiotic sensitivity among study patients who develop deep SSI. Study Design: Prospective Double Blinded Randomized Clinical Trial. This study will enroll 600 participants (300 in the control cohort, and 300 in the treatment cohort) enrolled over a four year period at a single Level I trauma center. The primary outcome variable will be presence or absence of SSI while secondary outcome variables will be bacterial speciation and antibiotic sensitivity in patients that develop SSI, and nonunion status determined at one year. Outcome variables will be evaluated and compared in both groups using both within and longitudinal analysis. The advantage of doing this pilot study at a single site is the ability to maintain uniformity in standard of care as management protocols for open fracture antibiotic prophylaxis and perioperative antibiotic prophylaxis are in place and will be followed. Impact and Military Benefit. This study has the potential to significantly reduce the incidence and burden of FRI after orthopaedic open fracture surgery. Military personnel are at a high risk for extremity high energy injuries, particularly open fractures. These injuries can occur during training, deployment, and outside of combat during leisure activities. Establishing the optimal ways to manage such injuries will help limit FRI, nonunions, and ultimate limb loss that deters military readiness. Our research will be used to obtain strategies that restore function and provide better outcomes for this honorable population, and will better allow for the injured personnel to return to duty and to recover as smoothly and quickly as possible.