Comparative effectiveness of prophylactic antibiotic regimens in preventing infection in open fractures: a prospective cohort study

Open fractures, particularly Gustilo-Anderson grade III injuries, carry high risks of infection. This cohort study compared the effectiveness of three prophylactic antibiotic regimens in reducing a range of infection-related outcomes, including infection markers (ESR, CRP), wound colonization, clinical infections, fever, cellulitis, and abscess formation. In this prospective cohort study, 600 patients aged 18–85 years with open fractures were enrolled at Shahid Bahonar Hospital, Iran (2020–2022). Participants were grouped by clinician-selected regimens: Group A (Cefazolin 1 g every 6 h + amikacin), Group B (Cefazolin 2 g every 8 h + amikacin), and Group C (Vancomycin 2 g every 12 h + amikacin). Multivariable logistic regression adjusted for confounders (age, fracture severity). Missing data (< 5%) were imputed. Of 978 patients screened, 600 completed follow-ups. Baseline demographics (mean age: 31.2 years; 82% male) were balanced. Group C had lower rates of elevated ESR (4.8% vs. 8.0% in Group A; adjusted RR = 0.61, 95% CI: 0.40–0.92), clinical infection (4.7% vs. 8.0%; RR = 0.58, CI: 0.38–0.89), and deep infection (2.7% vs. 5.3%; RR = 0.51, CI: 0.29–0.90). Minor adverse events (rash/nausea) were balanced across all groups (5.5% overall), with no significant differences in incidence or type between regimens. Vancomycin-amikacin was associated with reduced infection markers and complications compared to cefazolin regimens in this observational cohort, supporting its consideration in high-risk settings. Causality requires confirmation through randomized trials.