Purpose: In Gustilo grade III open fractures, it remains unknown which demographic or clinical features may be associated with an infection resistant to the administered prophylactic agent, compared to one that is susceptible. Methods: This was a retrospective case-control study on patients hospitalized from 2004 to 2009. Results: We identified 310 patients with Gustilo-III open fractures, 36 (12%) of which became infected after a median of tendays. In 26 (72%) of the episodes the pathogen was susceptible to the prophylactic antibiotic agent prescribed upon admission, while in the other ten it was resistant. All antibiotic prophylaxis was intravenous; the median duration of treatment was threedays and the median delay between trauma and surgery was oneday. In multivariate analysis adjusting for case-mix, only Gustilo-grade-IIIc fractures (vascular lesions) showed tendency to be infected with resistant pathogens (odds ratio 10; 95% confidence interval 1.0-10; p = 0.058). There were no significant differences between cases caused by antibiotic resistant and susceptible pathogen cases in patient's sex, presence of immune suppression, duration and choice of antibiotic prophylaxis, choice of surgical technique or materials, time delay until surgery, use of bone reaming, fracture localization, or presence of compartment syndrome. Conclusion: We were unable to identify any specific clinical parameters associated with infection with antibiotic resistant pathogens in Gustilo-grade III open fractures, other than the severity of the fracture itself. More research is needed to identify patients who might benefit from a broader-spectrum antibiotic prophylaxis
