Open fracture-related infection challenges persist in healthcare. From the time open fractures were defined ∼50 years ago, infection rates have gone essentially unchanged. Contributing factors include compromised vasculature, biofilm, and stalled innovations in treatment and prophylaxis. In this study, we engineered and tested the efficacy of a refillable drug delivery device, the Purgo Pouch (Pouch), that sustains local, high dose intrawound antibiotic concentrations in wound sites. We hypothesized that it would manage biofilm-compromised open fracture-related infection better than clinical standards of care. Therapies were tested in a unique sheep model of long bone open fracture-related infection with compromised tissue and biofilm inocula of methicillin-resistant