Adding Tobramycin to Vancomycin Fails to Reduce Infection Risk in Tibial Fracture Surgery: TOBRA Trial
USA: A large randomized clinical trial by the Major Extremity Trauma Research Consortium (METRC) has found that adding intrawound tobramycin to vancomycin powder does not provide additional benefit in preventing deep surgical site infections (SSIs) in patients undergoing surgery for periarticular tibial fractures. The findings, published in JAMA, suggest that the combination strategy is not superior to vancomycin alone, despite earlier evidence supporting the use of vancomycin powder in high-risk cases.
Surgical site infections remain a major concern in the management of periarticular tibial fractures, particularly in patients at elevated risk due to injury severity or comorbid factors. While intrawound vancomycin has been shown to reduce infection rates, it has been unclear whether combining it with another antibiotic, such as tobramycin, could further improve outcomes.
To explore this, researchers conducted the TOBRA randomized clinical trial, an open-label, assessor-masked study across 39 trauma centers in the United States. The trial enrolled adults with operatively managed tibial plateau or pilon fractures who were considered at high risk for infection. Participants were randomly assigned to receive either a combination of intrawound tobramycin (1.2 g) plus vancomycin (1.0 g) powder or vancomycin (1.0 g) powder alone at the time of definitive fracture fixation. Enrollment took place between June 2021 and December 2024, with follow-up completed in July 2025.
Out of 1,660 randomized patients, 1,528 were included in the primary analysis, with a mean age of 47 years and a majority being male. The primary outcome assessed was the occurrence of deep surgical site infection requiring surgical intervention within 182 days of fixation.
The trial revealed the following findings:
- Deep surgical site infections occurred in 7.4% patients in the combination therapy group.
- Deep surgical site infections occurred in 6.6% patients in the vancomycin-only group.
- No significant difference was observed between the two groups.
- The addition of tobramycin did not demonstrate superiority over vancomycin alone.
- Secondary outcomes showed no significant benefit with combination therapy.
- No advantage was observed in infections caused by gram-negative organisms.
- No advantage was observed in infections caused by gram-positive organisms.
- No benefit was seen in polymicrobial infections.
- No improvement was noted in rates of cellulitis treated with antibiotics.
These findings indicate that while intrawound antibiotic strategies remain important in reducing postoperative infections, adding tobramycin to vancomycin does not enhance protection against deep SSIs in this patient population. The results reinforce the role of vancomycin powder as a preventive measure but do not support routine use of combination intrawound antibiotics in this setting.
Overall, the study provides important evidence to guide clinical decision-making in orthopedic trauma care. It highlights the need for continued evaluation of infection prevention strategies while avoiding unnecessary interventions that do not improve patient outcomes.
Reference:
Major Extremity Trauma Research Consortium (METRC). Intrawound Tobramycin Plus Vancomycin to Prevent Surgical Site Infection in Tibial Fractures: The TOBRA Randomized Clinical Trial. JAMA. Published online April 15, 2026. doi:10.1001/jama.2026.4023
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