Randomized trial: local aqueous tobramycin did not reduce fracture-related infections versus IV antibiotics alone

# What the trial did Arun Aneja and colleagues randomized 569 patients with open extremity fractures requiring surgical fixation across three trauma centers. Patients were assigned to either receive a single 40 mL local aqueous tobramycin injection plus standard IV antibiotics (n = 285) or IV antibiotics alone (n = 284). Follow-up was a minimum of 6 months to assess fracture-related infection, nonunion rates, and bacterial organisms when infections occurred.

# Main result

# Who was studied Most injuries were high-energy mechanisms. Lower extremity fractures comprised the majority (76.7%), with upper extremities representing 31.7% (some patients had multiple sites). Gustilo-Anderson classification distribution was: 19.5% type I, 45.3% type II, 32% type IIIA, 1.8% type IIIB, and 1.4% type IIIC.

# How this compares with prior work Retrospective studies previously suggested local aqueous tobramycin could reduce deep surgical site infections. This randomized, prospective trial did not reproduce that benefit when using a stricter, prospectively applied definition of fracture-related infection.

# Practical implications for clinicians

• A single intraoperative aqueous tobramycin injection at the studied dose and delivery method should not be expected to reduce fracture-related infections beyond standard IV antibiotics based on these trial results.
• Unanswered operational questions remain: which local antibiotic formulations work best, how to achieve sustained local concentrations, how to target gram-negative organisms safely, and whether alternative delivery systems (e.g., carriers that prolong release) might change outcomes.
• The trial team indicated additional analyses will examine timing of IV antibiotics and other secondary outcomes, which may influence perioperative antibiotic strategies.

# What investigators said next Aneja noted that the trial raised more questions about optimal local antibiotic delivery methods and toxicity risks when attempting to target gram-negative bacteria. He also signaled forthcoming secondary analyses, including timing of IV antibiotic administration, which may offer actionable details for perioperative care.

# Bottom line In this randomized multicenter trial, adding a single intraoperative aqueous tobramycin injection to standard IV antibiotics did not reduce fracture-related infection risk compared with IV antibiotics alone. Clinicians should weigh current evidence when considering aqueous local tobramycin for open extremity fractures and follow upcoming secondary analyses for additional guidance.