Ceftriaxone Versus Piperacillin–Tazobactam Monotherapy for Open Fracture Prophylaxis: A Retrospective Cohort Study

OBJECTIVE: To compare rates of fracture-related infection (FRI) and acute kidney injury (AKI) in patients with open fractures treated with ceftriaxone (CTX) monotherapy or piperacillin-tazobactam (PIP-TAZ) monotherapy. DESIGN: Retrospective cohort study. SETTING: Single Level I Trauma Center (2020-2023). PATIENT SELECTION CRITERIA: Adults who sustained an open fracture of the femur, tibia, humerus, radius/ulna, and foot fractures (metatarsals, calcaneus, talus) and underwent operative irrigation and debridement. Exclusion criteria were less than 6 months of follow-up, hospital transfers, primary amputation, receipt of vancomycin within the first 48 hours in addition to CTX or PIP-TAZ, and cases requiring vascular bypass, rotational or free flaps, or full-thickness skin grafts. OUTCOME MEASURES AND COMPARISONS: Primary outcomes were rates FRI and AKI. Outcomes were compared between patients receiving prophylactic CTX versus PIP-TAZ monotherapy. RESULTS: A total of 156 patients with open fractures were identified, of which 136 met inclusion criteria: 67 treated with CTX monotherapy and 69 with PIP-TAZ monotherapy. The mean age was 46.2 years (range: 18-86) in the CTX cohort and 41.6 years (range: 19-83) in the PIP-TAZ cohort, and males comprised 56.7% and 72.3% of each group, respectively. Differences between groups were limited to a longer mean follow-up duration in the PIP-TAZ cohort ( P < 0.001) and a higher prevalence of soil contamination in the CTX cohort (11.9% vs. 1.4%, P = 0.015). There were no statistically significant differences in rates of FRI (25.4% CTX vs. 29.0% PIP-TAZ, P = 0.501) or AKI (11.9% vs. 15.9%, P = 0.636) between groups. On multivariate analysis, diabetes (OR 6.62, P = 0.003) was independently associated with increased FRI risk, whereas soil contamination (OR 3.42, P = 0.180) and external fixation (OR 1.92, P = 0.163) demonstrated nonsignificant trends toward higher risk. CONCLUSIONS: In this retrospective cohort of patients with open fractures, ceftriaxone and piperacillin-tazobactam demonstrated comparable outcomes in both fracture-related infection and acute kidney injury. Diabetes was found to be a statistically significant risk factor for FRI. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.