CEFAZOLIN AND THE R-1 SIDE CHAIN: WHY YOUR CEPHALOSPORIN-ALLERGIC JOINT ARTHROPLASTY PATIENTS CAN SAFELY BE GIVEN CEFAZOLIN FOR JOINT ARTHROPLASTY

Aim Cefazolin, a first generation cephalosporin, is the standard of care for perioperative antibiotic prophylaxis in hip and knee arthroplasty patients. Research has shown that prosthetic joint infection (PJI) rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis. Cefazolin contains an R1 side chain that has not shown cross reactivity with other cephalosporins. Despite these data, the declaration of a cephalosporin allergy causes uncertainty regarding the optimal antibiotic choice in these patients. The purpose of this study was to determine the safety of administering perioperative cefazolin in patients with a cephalosporin allergy undergoing joint arthroplasty. Methods We identified all patients (n=1267) with a documented cephalosporin allergy who underwent total hip or knee arthroplasty at a high volume academic medical center from 2016-2024. We compared patients who received perioperative cefazolin despite the presence of a cephalosporin allergy (n=481) to patients who received alternative antibiotic prophylaxis (n=786). The primary outcome measure was the incidence of IgE mediated allergic reactions within the first 72 hours postoperatively. Secondary outcomes included 90-day complication rates including PJI, C. difficile infection, adverse events and readmission. Results The incidence of allergic reaction in cephalosporin allergic patients who received cefazolin was 0.0% (0/481) compared to 0.51% (4/786) in patients who received alternative antibiotics prophylaxis (p=0.12). There were no significant differences in the incidences of PJI (0.23% vs. 0.30%; p=0.83), C. difficile infection (0.0% vs. 0.0%) or readmission (3.95% vs. 4.34%; p=0.75) within 90 days. There was one adverse event related to cefazolin administration which was urethral irritation and was self-limited. There were three adverse events related to alternative antibiotic prophylaxis including cutaneous manifestations, GI distress and headache in a patient with idiopathic intracranial hypertension. All four allergic reactions in the alternative antibiotic prophylaxis cohort required supportive treatment with IV corticosteroids, fluids and antihistamines. Conclusion In this cohort of hip and knee arthroplasty patients, cefazolin administration in the setting of a cephalosporin allergy resulted in a 0.0% incidence of IgE mediated allergic reactions. These data and the fact that cefazolin's unique R1 side chain is not shared by any other cephalosporins suggests that cefazolin can safely be administered to most patients with a documented cephalosporin allergy.