Intrawound Tobramycin Plus Vancomycin in Tibial Fracture Fixation

Key Takeaways

• Deep surgical site infection probabilities at 182 days were 7.4% with tobramycin plus vancomycin and 6.6% with vancomycin alone.
• The multicenter randomized trial at 39 US trauma centers compared intrawound tobramycin 1.2 g plus vancomycin 1.0 g with vancomycin 1.0 g alone at definitive fixation.
• Secondary outcomes, including infection subtype categories and cellulitis or skin infections treated only with antibiotics, also did not meet the superiority threshold.

In the TOBRA randomized clinical trial, adults with periarticular tibial fractures received intrawound tobramycin plus vancomycin or vancomycin alone at fixation, and the hazard ratio for deep infection was 1.11. The trial compared local antibiotic powder strategies used during definitive fracture fixation and assessed whether adding aminoglycoside powder improved outcomes beyond vancomycin alone. The prespecified superiority threshold was not met, and adding intrawound tobramycin was not superior to vancomycin alone for the primary outcome.

The open-label, assessor-masked randomized clinical trial was conducted at 39 US trauma centers. Eligible adults had operatively treated periarticular tibial fractures, including tibial plateau or pilon injuries, and met 1 of 3 elevated infection-risk criteria. Investigators compared intrawound tobramycin 1.2 g plus vancomycin 1.0 g powder with intrawound vancomycin 1.0 g powder alone, applied at definitive fixation. Enrollment ran from June 18, 2021, through December 12, 2024, and final follow-up occurred on July 15, 2025. Among the 1528 participants included in the primary analysis, mean age was 47.0 years, 39.5% were female, and 60.5% were male; 1660 participants were randomized overall.

The primary outcome was deep surgical site infection requiring surgical management within 182 days of definitive fracture fixation. The primary analysis included 1528 of 1660 randomized participants. Deep surgical site infections occurred in 51 of 753 participants, 7.4%, with tobramycin plus vancomycin and 47 of 775 participants, 6.6%, with vancomycin alone. The hazard ratio was 1.11, with a 95% Bayesian credible interval of 0.75 to 1.66 and a posterior probability of superiority of 29.7%, which did not meet the prespecified threshold.

Secondary outcomes included gram-negative-only infections, gram-positive infections, polymicrobial cultures, negative cultures, and cellulitis or skin infections treated only with antibiotics. The threshold required for superiority was not reached for any secondary outcome. These measures addressed infection subtype patterns and antibiotic-treated superficial presentations without changing the main comparison.

Investigators concluded that adding intrawound tobramycin to vancomycin did not reduce deep surgical site infection in this enrolled population.