Effect of Extended Prophylactic Antibiotic Duration in the Treatment of Open Fracture Wounds Differs by Level of Contamination

To determine the association between prophylactic antibiotic duration after the definitive wound closure of an open fracture and deep surgical site infection (SSI). Retrospective cohort study. 41 clinical sites in the United States, Canada, Australia, Norway, and India. Patients (N = 2400) with open fractures of the extremities who participated in the Fluid Lavage of Open Wounds (FLOW) trial. Extended antibiotic prophylaxis, defined as more than 72 hours of continuous antibiotic use after definitive wound closure. Deep SSI diagnosed within 1 year of enrollment. Forty-two percent of participants received extended antibiotic prophylaxis. Deep SSI prevalence was 5%, 8%, and 23% for wounds with mild, moderate, and severe contamination, respectively. In open fractures with mild contamination, extended antibiotic use showed a trend toward increased odds [adjusted odds ratio (aOR) = 1.39; 95% confidence interval (CI), 0.92-2.11] of deep SSI compared with shorter use. No association was found among patients with moderate contamination (aOR = 1.09; 95% CI, 0.53-2.27). By contrast, extended antibiotic prophylaxis was strongly protective (aOR = 0.20; 95% CI, 0.07-0.60) against deep SSI in patients with severe contamination. Propensity score sensitivity analysis results were consistent with these findings. The evidence suggests differential effects of extended postclosure antibiotic duration on SSI odds contingent on the degree of contamination in open fracture wounds. Although extended antibiotic duration resulted in lower odds of SSI among patients with severely contaminated wounds, we observed a trend toward higher odds of SSI in mildly contaminated wounds. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.