Does Prophylactic Local Tobramycin Injection Lower Open Fracture Infection Rates?
Abstract
Open fractures are defined as injuries in which the broken bone communicates with the outside environment. They have a very high rate of developing wound infections because the soft tissue envelope is disrupted, the blood vessels that provide nutrition and antibiotics are damaged, and there are minimal defenses against bacteria. The standard of care (SOC) for treating such injuries consists of immediately providing systemic antibiotics via an intravenous route, performing a formal irrigation, and debridement in the operating room along with fixing the fracture with an orthopaedic implant. Local antibiotic delivery implies depositing antibiotics at the site of the open fracture, which has the benefit of giving a higher bactericidal dosage of antibiotic directly to the site where bacteria might propagate without concern for toxicity to surrounding organs. The proposed study will test the utility of delivering a safe, validated dosage of local antibiotic (tobramycin) that has a different mechanism of action than the antibiotic delivered systemically (cephalosporin). By combining two different forms of antibiotics with two different mechanisms of action, the treatment becomes more potent and has a wider spectrum of activity against multiple different types of bacteria. The proposed study will assess whether adding local aqueous tobramycin to the SOC will result in fewer fracture-related infections (FRI) without any negative consequences on bone healing (or bone union) in open extremity fractures (OEF). In addition, this study will also investigate and define the types of bacteria that will grow when SOC if performed and when local tobramycin adjunct is added to the SOC. The local tobramycin adjunct combination treatment has been shown to work in animal studies and poorly designed retrospective clinical studies. The proposed study will provide the highest-based evidence in the form of a randomized clinical trial in the focus area of FRI with translation of early findings. Accordingly, 600 patients with OEF at two busy trauma hospitals will be enrolled over 3 years, with the final year dedicated to the interpretation of the data. Half of the patients will receive SOC plus placebo local injection (control group), while the other half will receive SOC plus local tobramycin injection (treatment group). The results of interest will include the rate of FRI, the rate of fracture nonunion, and the type of bacteria that grow along with their antibiotic resistance profile in each group. The authors hypothesize that the treatment group will have lower rates of FRI without any negative consequence on bone union and fewer gram-negative and Staphylococcus bacteria growth than the control group. This study has the potential to help all patients that obtain OEF in the military as well as the civilian sector. If a patient with OEF develops FRI, this results in greater physical and emotional patient morbidity with increased reoperations and higher rate of limb amputation. Therefore, if this study is able to demonstrate a lower rate of FRI without negative consequence on bone union or even provide data on the different bacteria that grow in each study arm (control or treatment), it will advance medical care for OEF. Establishing the optimal way to treat FRI via collecting high-quality data will have a tremendous impact on patient health by limiting limb loss and benefiting work readiness. This research will be used to obtain strategies that restore function and provide better outcomes to the military and civilian population by helping the injured personnel return to duty and recover as smoothly and quickly as possible. The low cost and simplicity of the local tobramycin intervention will allow immediate implementation in clinical practice in both military and civilian settings.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110833
Entities
People
- Arun Aneja
Organizations
- United States Army
- University of Kentucky