Efficacy of Ceftriaxone vs Cefazolin With or Without Gentamicin in Grade III Open Fractures

Introduction: The Gustilo-Anderson classification system categorizes open fractures into grades I-III based on wound size, contamination, and skeletal injury. According to EAST guidelines, grade III carries the highest risk of infection at 24% and warrant prophylaxis with gram-positive and negative coverage. While no specific agent is endorsed, our health system recommends cefazolin plus gentamicin in the emergency department (ED). Guidelines also advise the initiation within 1 hour of ED arrival or 3 hours of injury to decrease infection risk. Given the urgency, ceftriaxone may serve as a potential alternative, offering similar coverage, standard dosing, easy accessibility, and favorable safety profile. The purpose of this study was to compare treatment failure rates of grade III open fractures managed with cefazolin plus gentamicin versus ceftriaxone.


Methods: A multi-centered retrospective study was conducted at Advocate Health from January 1st, 2022, to December 31st, 2023, in patients with grade III open fractures of long bones. Treatment failure was defined using The Centers for Disease Control’s definition of surgical site infection within 90 days of injury. Exclusion criteria included antibiotics for alternative indication, outside hospital (OSH) management, OSH transfer, death unrelated to infection, fractures reclassification or other antibiotic.


Results: A total of 71 patients were included, (cefazolin = 57; ceftriaxone = 14). Despite recommendations, 71.9% of cefazolin patients did not receive an aminoglycoside in combination. Baseline characteristics were not statistically different. The primary outcome of treatment failure was higher in the cefazolin cohort but not statistically significant (22.8% vs. 14.3%; P=0.48). Time of first antibiotic dose was faster in the ceftriaxone cohort (48 minutes vs 30 minutes; P=0.03), with a trend toward more receiving antibiotics within 1 hour (P=0.08). Time to debridement was also shorter with ceftriaxone (8h vs 3.8h; P=0.02). Acute kidney injury was more common in the ceftriaxone cohort (9.3% vs 28.6%; P=0.01).


Conclusions: Infection rates did not differ between groups; however, ceftriaxone was associated with improved timing measures, which are linked to better clinical outcomes. This suggests potential benefit that warrants further investigation.