Safety of topical tobramycin powder during operative treatment of fractures.

Abstract

Background: Despite its common practice, limited data exists on the pharmacokinetics and safety of topical tobramycin in fracture fixation surgery. This study aimed to evaluate the nephrotoxicity risk, systemic absorption, and clearance of topical tobramycin powder after application in tibial fracture wound beds.

Methods: This prospective, observational safety study was nested within a randomized controlled trial 'Topical Antibiotic Therapy to Reduce Infection After Operative Treatment of High-Risk Infection (TOBRA)' (ClinicalTrials.gov ID #NCT04597008). Patients randomized to the treatment arm were administered topical vancomycin (1000 mg) and tobramycin (1200 mg) directly in the wound bed at the time of definitive fixation. The study included consecutive patients allocated to the treatment arm at a single trial site. The primary outcome was a change in renal function post-treatment, using the acute kidney injury network (AKIN) criteria.

Results: A total of 64 patients were enrolled. The median age of participants was 49 years and 39% were female. Using available data, 97% of patients did not experience acute kidney injury. Two patients were classified as AKIN stage 1 at 24 h after treatment; both patients' serum creatinine returned to baseline levels at the 2-week measurement. Median peak tobramycin serum level was 2.5 mcg/mL (IQR 1.3, 4.3). All patients had a serum tobramycin level <2 mcg/mL at 24-h post-treatment.

Conclusions: A single dose of 1200 mg tobramycin powder administered locally during fracture fixation of the tibia does not lead to nephrotoxic serum levels or long-term changes to renal function.