Tobramycin Added to Vancomycin Shows No Extra Benefit in Preventing Tibial Fracture Surgical Infections: TOBRA Trial
USA: A large multicentre randomized clinical trial published in JAMA has found that adding intrawound tobramycin powder to vancomycin does not provide additional benefit in preventing deep surgical site infections (SSIs) in patients undergoing surgery for periarticular tibial fractures.
The study, led by Robert V. O’Toole from the Department of Orthopaedics at the R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, evaluated whether combining two antibiotics applied directly at the surgical site could better reduce infection risk compared with vancomycin alone.
Periarticular tibial fractures, including tibial plateau and pilon fractures, are associated with a high risk of postoperative infection, particularly in complex trauma cases requiring surgical fixation. Intrawound vancomycin powder has previously been shown to reduce infection risk, prompting interest in whether adding a second antibiotic such as tobramycin could further improve outcomes by broadening antimicrobial coverage.
The open-label, assessor-masked trial was conducted across 39 trauma centers in the United States between June 2021 and December 2024. A total of 1,660 adults with operatively treated periarticular tibial fractures were randomized, and 1,528 patients were included in the final analysis. Participants were assigned to receive either intrawound vancomycin (1.0 g) alone or a combination of vancomycin (1.0 g) plus tobramycin (1.2 g) applied at the time of definitive surgical fixation.
The primary endpoint was the occurrence of deep surgical site infection requiring surgical intervention within 182 days after surgery. Researchers also evaluated secondary outcomes, including infections caused by different bacterial types and cases treated with antibiotics alone.
Key findings from the trial include:
- Deep surgical site infections occurred in 7.4% of patients in the tobramycin-plus-vancomycin group.
- In the vancomycin-only group, infection rates were 6.6%.
- There was no statistically meaningful difference between the two groups.
- The hazard ratio for infection with combination therapy was 1.11, indicating no reduction in risk.
- The probability that the combination therapy was superior was only 29.7%, well below the threshold required for clinical benefit.
- No secondary outcomes showed improvement with the addition of tobramycin.
Overall, adding intrawound tobramycin to vancomycin did not reduce deep surgical site infections compared with vancomycin alone in high-risk patients.
The trial was large and well designed, but its open-label nature introduces a theoretical risk of bias, although infection outcomes are largely objective. The study population included only high-risk fracture cases, which may limit applicability to broader orthopedic settings. A minor baseline difference in diabetes prevalence between groups was observed, but sensitivity analyses showed it did not influence the results.
Additionally, some infections may occur beyond the 182-day follow-up period; however, researchers noted that this is unlikely to change the overall findings.
"The study provides strong evidence that intrawound tobramycin offers no added benefit over vancomycin alone in preventing deep infections after tibial fracture surgery, supporting vancomycin monotherapy as an effective prophylactic approach in this setting," the authors concluded.
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. 2026;335(18):1586–1595. doi:10.1001/jama.2026.4023
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