2025 Southeastern Residency Conference

Cefazolin Plus Metronidazole Compared to Cefoxitin Alone for Surgical Prophylaxis in Hysterectomies
Tristan Jernigan, Austin Roberts, Kendra Spilkin, Benjamin Casey
Background: Antibiotic prophylaxis is a critical component of surgical site infection prevention in hysterectomy procedures. The 2013 IDSA guidelines recommend cefazolin, cefoxitin, or ampicillin-sulbactam as first-line agents, administered within one hour prior to surgical incision. When choosing between the guideline recommendations it is important to consider reported efficacy and the logistical implications of different regimens. Cefazolin is redosed every four hour while cefoxitin is redosed every two hours. In a 2017 study by Till and colleagues, cefazolin combined with metronidazole reduced the incidence of post-operative infections compared to cefoxitin alone in hysterectomy patients. Based on these findings, our institution transitioned from cefoxitin to a cefazolin plus metronidazole regimen in May 2022. This study evaluated the impact of this change on compliance with surgical prophylactic antibiotic administration, focusing on whether this transition increased appropriate prophylaxis rates by leveraging cefazolin’s longer dosing interval to reduce the incidence of missed or delayed prophylactic doses.
Methods: This was a single-center, retrospective, pre and post implementation cohort study of adult patients who underwent a hysterectomy between November 15th, 2021 and November 14th, 2022. Patients were identified by a generated list of patients who underwent a hysterectomy during the designated time frame and were randomized. Patients were included if prophylactic antibiotics were administered. Patients were excluded based on extremes of age or if clindamycin and gentamicin were administered for surgical prophylaxis. The primary endpoint was the percentage of patients who received appropriate antimicrobial surgical prophylaxis. Appropriate prophylaxis was defined as preoperative administration within one hour of surgical incision and subsequent redosing within thirty minutes of the recommended frequency. The secondary endpoints included the incidence of post-operative infection, direct drug cost with each regimen, and a subgroup analysis of the primary outcome to evaluate reasons for inappropriate prophylaxis. 
Results: A total of 260 patients were screened, and 226 (n = 140 cefoxitin, n = 86 cefazolin plus metronidazole) met criteria for our study. Patients who received clindamycin plus gentamicin for surgical prophylaxis (n=34) were excluded from the primary and secondary endpoints. Baseline characteristics were similar between the two groups. Cefoxitin was associated with significantly higher appropriate prophylaxis rates when compared to cefazolin plus metronidazole (88.6% vs. 76.8%, p=0.009). There was no significant difference in post-operative infections between the two groups (0.4% vs. 0%, p=0.32). Subgroup analysis of the primary outcome found significantly more cases of inappropriate dosing in the cefazolin plus metronidazole group (4.7% vs 0%, p=0.02) and significantly more cases of redosing errors with cefoxitin (2.9% vs. 0%, p=0.04).
Conclusion: While cefoxitin was associated with higher rates of appropriate prophylaxis, the primary reason for inappropriate prophylaxis in the cefazolin plus metronidazole group was the use of cefazolin alone for prophylaxis, which is an appropriate, guideline-recommended prophylaxis regimen. Cefoxitin was associated with a higher rate of redosing errors when compared to cefazolin plus metronidazole. Overall rates of post-operative infection were low, with no significant difference being observed between the two groups. 
Disclaimer: This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.