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Antibiotic prophylaxis for open lower extremity fractures: a comparative propensity-scored matched analysis of cefazolin vs. piperacillin-tazobactam
Journal article   Peer reviewed

Antibiotic prophylaxis for open lower extremity fractures: a comparative propensity-scored matched analysis of cefazolin vs. piperacillin-tazobactam

Kush S. Mody, Anish K Ponna, Ryan T Santilli, Andrew Laychur, Joseph D Galloway, Mark Adams, Mark Reilly and Sheldon S. Lin
Archives of Orthopaedic and Trauma Surgery, v 146(1), 166
29 Apr 2026
DOI: https://doi.org/10.1007/s00402-026-06333-0
PMID: 42053819
Featured in Collection :   Research Supported by Drexel Libraries' OA Programs
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https://doi.org/10.1007/s00402-026-06333-0View
Published, Version of Record (VoR) Open Access via Drexel Libraries Read and Publish Program 2026 Restricted CC BY V4.0

Abstract

Open fractures Antibiotic prophylaxis Cefazolin Piperacillin-tazobactam
Introduction Optimal antibiotic prophylaxis for open fractures remains controversial, particularly regarding whether broader-spectrum regimens offer clinical advantages over cefazolin monotherapy. Despite guideline recommendations supporting first-generation cephalosporins for most open fractures, many centers routinely administer piperacillin-tazobactam. This study aims to evaluate differences in postoperative outcomes between cefazolin and piperacillin-tazobactam in lower extremity open fractures across all Gustilo-Anderson types. Materials and methods This retrospective cohort study was performed using the TriNetX database to identify adult patients with Gustilo-Anderson type I-III lower extremity open fractures who received either cefazolin or piperacillin-tazobactam. 1:1 propensity score matching controlled for age, sex, demographics, and relevant comorbidities. Outcomes were assessed at 90 days and 1 year using risk ratios (RR) with corresponding 95% confidence intervals. Results A total of 47,692 patients met inclusion criteria prior to matching. After matching, 1,527 patients remained in each treatment group for the combined type I/II/III cohort and similar matched pairs were obtained for type I/II and type III subgroups. At 90 days, cefazolin was associated with significantly lower rates of surgical site infection (RR 0.569), osteomyelitis (RR 0.292), sepsis (RR 0.244), reoperation (RR 0.474), readmission (RR 0.518), thromboembolic events (RR 0.480), AKI (0.448), and mortality (RR 0.208) across most analyses. Nonunion/malunion rates were similar between groups for type I/II and the combined cohort (p > 0.05), but higher among type III fractures treated with cefazolin (RR1.933). At 1 year, cefazolin was associated with significantly lower reoperation (RR 0.564), implant removal (RR 0.585), and mortality (RR 0.298) across all analyses, with persistently higher nonunion/malunion risk in type III fractures (RR 1.929). Conclusion Cefazolin was associated with comparable or superior outcomes to piperacillin-tazobactam for most postoperative complications following lower extremity open fractures. These findings support current guideline-aligned stewardship practices and question the routine use of broader-spectrum prophylaxis, particularly outside specific contamination scenarios. Level of evidence III – Retrospective Comparative Study.

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