One Intrawound Antibiotic Wins for Surgical Infections After Tibial Fracture Surgery

Pairing intrawound tobramycin with vancomycin powder was no better than vancomycin alone at preventing deep surgical site infections among patients with periarticular tibial fractures at high risk of infection, the randomized TOBRA trial showed.

Among over 1,500 patients, those in the combination treatment group had a 7.4% probability of deep surgical site infection within 182 days compared with a probability of 6.6% in the control group (HR 1.11, 95% credible interval 0.75-1.66), reported Robert O’Toole, MD, of the University of Maryland School of Medicine in Baltimore, and colleagues.

The combination therapy’s posterior probability of being superior to vancomycin alone was only 29.7%, the researchers noted in JAMA.

These findings “contradicted” current practice trends and the expected benefit of adding tobramycin in this setting, O’Toole and team wrote.

A previous trial from the same group of researchers suggested that 1 g of vancomycin powder applied to the surgical incision during closure of definitive fixation reduced the risk of gram-positive surgical site infections, but had no effect on gram-negative infections, which are fairly common in this setting.

On the other hand, tobramycin is effective against a wide range of gram-negative pathogens. Orthopedic surgeons commonly use the antibiotic combination intraoperatively to reduce infection risk, but research backing the approach’s clinical benefit and safety are limited, the authors explained.

“Based on the observed data, it is unlikely that the combination of tobramycin and vancomycin powder is superior to vancomycin powder alone in preventing surgical site infection after tibial fracture, and it is highly improbable that this combined prophylaxis provides the hypothesized benefit,” they wrote.

Conducted at 39 U.S. trauma centers, the open-label TOBRA trial enrolled patients with periarticular tibial fractures treated with plate and screw fixation who met one of three criteria for high risk of infection from June 2021 to December 2024. Of the 1,528 patients included in the primary analysis (mean age 47, 60.5% men), 56% had tibial plateau fractures, 44% had tibial pilon fractures, and 19.8% had open fractures.

Patients were randomized 1:1 to receive 1-g vancomycin powder applied to the wound at closure with or without 1.2-g tobramycin powder.

The study’s primary outcome was a deep surgical site infection that required operative debridement within 182 days of surgery, which occurred in 51 of 753 participants in the combination treatment group and 47 of 775 participants in the vancomycin-alone group.

There were no differences between groups in secondary outcomes including 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.

Study limitations included the trial’s unmasked design, which could have introduced bias. The findings may not be generalizable to patients undergoing surgery who aren’t at high risk of infection. In addition, about 25% of deep surgical site infections presented more than 182 days after surgical fixation.