Local Application of a Gentamicin-Loaded Hydrogel Early After Injury Is Superior to Perioperative Systemic Prophylaxis in a Rabbit Open Fracture Model.

Open fractures are at significant risk of developing a fracture-related infection, despite the routine administration of perioperative antibiotic prophylaxis. Early application of antibiotic prophylaxis is known to reduce infection rates; however, most international guidelines focus on postoperative duration rather than prehospital administration. We compared conventional perioperative prophylaxis against early prehospital prophylaxis either as a systemic single shot of cefuroxime or a locally applied gentamicin-loaded hydrogel in a laboratory animal model. Thirty New Zealand white rabbits underwent a first surgical procedure to create an open wound, bone damage and contamination with Staphylococcus aureus. After a 4-hour observation period mimicking the time-to-treatment, the animals underwent a second procedure to irrigate the wound and apply a fracture fixation device. The 5 groups (n = 6 per group) received (1) no treatment; (2) conventional 24-hour cefuroxime; (3) an early single shot of cefuroxime 15 minutes after trauma; (4) a combined early and standard systemic prophylaxis; and (5) early application of a gentamicin-loaded hydrogel that was removed during irrigation. Untreated animals displayed high numbers of bacteria in irrigation fluid and were all highly culture positive at euthanasia. Three of 6 animals were culture positive at euthanasia after conventional prophylaxis. Early systemic prophylaxis reduced bacterial burden in irrigation fluid by up to 100-fold, but 5/6 animals were culture positive at euthanasia. The combined prophylaxis displayed greater efficacy with only 1/6 rabbits culture positive at euthanasia. Local application of the gentamicin-loaded hydrogel reduced bacteria recovered by irrigation to just above our detection limit, and at euthanasia, all animals were culture negative at euthanasia. Early systemic antibiotic administration can significantly reduce bacterial burden in the operative field and reduce culture positivity at euthanasia when continued for 24 hours after injury. The early application of a gentamicin-loaded hydrogel that was removed during irrigation displayed superior efficacy to early systemic therapy alone and postoperative conventional gold standard 24-hour systemic therapy alone. These experimental results highlight the importance of early antibiotic administration in fracture care.