A Randomized Controlled Trial Evaluating Locally Administered Gentamicin in the Prevention of Deep Infection after Open Tibial Shaft Fractures in Tanzania

Investigator: David Shearer, MD
Sponsor: Hellman Family Foundation

Location(s): Tanzania


Tibial shaft fractures are the most common long-bone fracture and most likely to present with a traumatic open wound overlying the fracture. Deep infection remains a common, devastating complication of open injuries leading to lifelong impairment that disproportionately affects low-and middle-income countries (LMICs).Thorough surgical debridement, followed by fracture stabilization using internal or external fixation, is the mainstay of treatment. One proposed adjunctive measure is prophylactic local antibiotic delivery, which can achieve much higher antibiotic concentrations at the surgical site than can be achieved safely with systemic administration. There is a growing body of literature evaluating local antibiotic administration in both aqueous and powder form at the time of wound closure. While demonstrating potentially promising results, these studies are heterogeneous, of poor methodologic quality, and none originate from LMICs where this technique would have the greatest potential benefits. Local gentamicin is particularly promising given the broad spectrum of activity against common pathogens in osteomyelitis (staphylococcus, gram-negative rods), wide availability, and low cost (<1$ per 80mg vial). We are planning a prospective randomized controlled trial enrolling all adults with open tibial shaft fractures at the Muhimbili Orthopaedic Institute in Dar es Salaam, Tanzania, as part of an ongoing partnership with the UCSF Department of Orthopaedic Surgery. Participants will be randomly assigned to receive aqueous gentamicin administered after closure or placebo saline injection. The primary outcome will be deep surgical site infection within 1 year. The primary outcome will be deep surgical site infection within 1 year. Secondary outcomes include health-related quality-of-life (HRQOL) as measured by EQ-5D, modified Radiographic Union Scale for Tibial Fractures (mRUST), FIX-IT score for clinical healing, and the direct and indirect cost of treatment using time-driven activity-based costing (TDABC) and survey methods, respectively. Our central hypothesis is that deep infection has significant clinical and economic impact on patients with open tibial fractures, and the risk of deep infection will be affected by prophylactic use of locally-administered antibiotics. If efficacious, local antibiotics would be a highly cost-effective secondary prevention strategy in LMICs. Furthermore, although these findings will originate from an LMIC, results would be applicable to populations in both high and low-income countries. Therefore, a risk reduction on par with current literature could significantly reduce the global burden of open fracture.