Antibiotic Duration Beyond 24 Hours Does Not Reduce Infection in Grade 3 Open Extremity Fractures

Authors:
Andrea Gochi, Henry Olivera Perez, Anna Huang Perez, Hyunjee Kwak, Lucas Thornblade, Naveen Balan, Adam Gutierrez, Genna Beattie, Gregory Victorino, April Mendoza

Body of Abstract:
Background: Grade 3 Gustilo Anderson open extremity fractures carry a high risk of infection, yet wide variation in antibiotic duration persists. Many patients receive a prolonged (> 48 hour) antibiotic course despite limited evidence of benefit. Prior studies have demonstrated no reduction in surgical site infection (SSI) with broader antibiotic coverage in severe open fractures, and in some cases increased nephrotoxicity with longer regimens. We hypothesized that antibiotic administration beyond 24 hours from time of injury, provides no additional protection against development of SSI in Grade 3 open extremity fractures.

Methods: A retrospective cohort study of all adult Grade 3 Gustilo Anderson open extremity fractures treated at a Level I trauma center from October 2019 to September 2025 was conducted. Clinical characteristics, antibiotic treatment data, and infectious outcomes were collected. The primary outcome was development of a SSI (superficial or deep) at the site of Grade 3 open extremity injury. The secondary outcome was need for hardware removal. Multivariable logistic regression was used to identify independent predictors of SSI, and a separate model evaluated factors associated with hardware removal.

Results: Out of 1507 Grade 1-3 open extremity fractures, a total of 216 Grade 3 open extremity fractures, met inclusion criteria. Patients with incomplete data, those who died on arrival or died within 2 weeks were excluded from analysis. The overall SSI incidence was 18.5% (40/216), including 15 superficial SSI and 25 deep SSI infections, with 43% of the cohort receiving broad coverage (Gram positive and Gram negative and/or anaerobic coverage). Infection rates did not differ between patients receiving ≤24 hours versus >24 hours of total antibiotics (20.9% vs 17.9%, p=0.649). Postoperative antibiotic duration was similarly not associated with infection and neither was coverage type (all p>0.05). No significant relationship was found between antibiotic duration and hardware removal (p>0.05). In multivariable analysis, active smoking (OR 4.47, p=0.004), diabetes mellitus (OR 5.12, p=0.018) and need for multiple washouts (OR 3.89, p=0.013), were independently associated with SSI. In the hardware removal model, superficial SSI (OR 6.60, p=0.022) was the strongest contributor.

Conclusions: Antibiotic administration beyond 24 hours for Grade 3 Gustilo Anderson open extremity fractures provided no protective benefit against SSI or need for hardware removal. These findings support emerging evidence that prolonged antibiotic courses may not improve outcomes in severe open fractures and reinforce the need for antibiotic stewardship in the management of Grade 3 injuries.