Intrawound tobramycin plus vancomycin did not reduce deep infection risk compared with vancomycin alone in high-risk tibial fractures

This randomized clinical trial enrolled 1660 adults with an operatively treated periarticular tibial fracture, either tibial plateau or pilon, who met one of three criteria for elevated infection risk. The study was conducted across 39 US trauma centers. Participants received definitive fixation at the time of intervention. The primary exposure was the addition of intrawound tobramycin powder to intrawound vancomycin powder delivered during surgery. The comparator group received intrawound vancomycin powder alone. Both groups received the powder at the time of definitive fracture fixation.

The primary outcome was deep surgical site infection requiring surgical management within 182 days of definitive fracture fixation. The rate of this outcome was 7.4% in the tobramycin plus vancomycin group versus 6.6% in the vancomycin alone group. Specifically, 51 of 753 participants in the tobramycin plus vancomycin group experienced the primary outcome, while 47 of 775 participants in the vancomycin alone group experienced it. The effect size was a hazard ratio of 1.11. The 95% Bayesian credible interval for this hazard ratio ranged from 0.75 to 1.66. The posterior probability of superiority was 29.7%. These data indicate no reduction in the primary outcome with the addition of tobramycin.

Key secondary outcomes included deep surgical site infections with pathogens that were gram-negative only, deep surgical site infections with at least one pathogen that was gram-positive, deep surgical site infections with polymicrobial cultures, deep surgical site infections with negative culture results, and cellulitis or skin infections treated only with antibiotics. The study report did not provide specific numerical results for these secondary outcomes in the provided data. The analysis focused on the primary composite of deep infection requiring surgical management.

Safety and tolerability findings were not reported in the provided data. There were no reported adverse events, serious adverse events, discontinuations, or specific tolerability metrics. The study design was open-label with assessor-masked assessment of outcomes. Funding or conflicts of interest were not reported. The absence of safety data limits the ability to assess the risk-benefit profile of adding tobramycin powder in this specific population.

Prior landmark studies in orthopedic infection prevention have often focused on vancomycin powder as a standard adjunct. This trial suggests that adding tobramycin does not confer additional benefit over vancomycin alone for preventing deep surgical site infections in high-risk tibial fractures. The hazard ratio of 1.11 suggests a potential trend toward higher risk, although the Bayesian credible interval includes values below 1.0. The posterior probability of superiority was low at 29.7%, indicating that the data do not support the efficacy of the combination therapy for the primary endpoint.

Methodological limitations include the open-label nature of the trial, which may introduce performance bias, although assessors were masked. The sample size of 1660 participants across 39 centers provides a robust estimate for the primary outcome. However, the lack of reported safety data is a significant limitation. Potential biases related to the open-label design and the specific criteria for elevated infection risk may influence generalizability to other fracture types or risk profiles.

Clinical implications suggest that adding intrawound tobramycin powder to vancomycin powder at the time of definitive fixation did not reduce deep surgical site infections compared with vancomycin powder alone. Physicians should not alter their standard practice of using vancomycin powder alone based on these results. The data do not support the routine addition of tobramycin for this indication. Further research may be needed to identify subgroups that might benefit from combination therapy or to clarify safety concerns.

Questions remain unanswered regarding the safety profile of the combination therapy, as adverse events were not reported. It is unclear if the lack of efficacy extends to other fracture types or lower-risk populations. The study did not address long-term outcomes beyond 182 days. Clinicians should continue to follow established protocols for infection prevention in periarticular tibial fractures without assuming added benefit from tobramycin.