Novel Topical Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: TOBRA-A Multicenter RCT
Abstract
This application is directly responsive to the Fiscal Year 2018 PRORP CTA Focus Area of “Surgical Techniques and Outcomes,” in the Surgical Care Area of Extremity Fractures. In addition, the proposed intervention, by substantially reducing the rate of the most prevalent orthopaedic complication resulting in poor outcomes following trauma, would directly address the special focus area of allowing patients to more quickly return to duty/work. Infection after treatment of high-energy military fractures is very common and continues to cause significant morbidity. Recently, a study showing use of local vancomycin powder around the metal hardware used to treat these at-risk fractures results in a reduced risk of infection. The powder is thought to create a kill zone around the metal, prevent bacterial colonization, and therefore reduce the rate of postoperative infection. This study seeks to expand upon the findings of this previous work and expand the potential antibiotic coverage by adding local tobramycin powder to the treatment regimen. Treatment of patients with this new technique aimed at delivering both vancomycin and tobramycin antibiotics locally in addition to standard-of-care treatment will reduce infection compared to patients who are only treated with the standard of care and local vancomycin. Our primary specific aim is to demonstrate that the infection rate (defined by Centers for Disease Control and Prevention criteria) is lower in patients with at-risk fractures treated with the standard of care as well as local vancomycin and tobramycin than patients treated with the standard of care and vancomycin alone. Additional specific aims include investigating the potential development of antibiotic resistance, examining bacterial sensitivities in patients who become infected in the treatment group, and comparing the proportion of additional complications such as wound dehiscence and nonunion. The proposed study is a multi-center, prospective, blinded, randomized controlled trial. The study will use the Department of Defense-funded Major Extremity Trauma Research Consortium to accumulate patients from 29 core civilian and 1 military center to insure the highest quality of data collection, analysis, and scientific integrity. The study group will be high-energy tibial plateau, pilon, and calcaneus fractures treated with a plate and screw fixation in a staged fashion, as this patient population has been shown to have a high infection rate and is amenable to the existing technology. Nineteen hundred participants (950 per treatment arm) will be enrolled from METRC trauma centers over a 24-month period. Participants will be recruited during hospitalization for the initial injury. Infection is a very common and serious complication associated with treatment of high-energy military extremity trauma. Fixation of fractures in these injuries involves the use of metal implants. Plates and screws become colonized with bacteria and lead to high rates of infection that are not treated well with intravenous antibiotics. If the proposed study demonstrated the utility of this technology, it would have a dramatic effect on reducing the morbidity associated with extremity trauma. Further, a positive result could revolutionize the approach to prophylaxis against surgical site infection after orthopaedic fracture care in both the military and civilian arenas by moving the field toward technologies that focus on local antibiotics associated with the implanted devices.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910848
Entities
People
- Robert Otoole
Organizations
- United States Army
- University of Maryland, Baltimore