Cefazolin and the R1 Side Chain: Why Patients with a Cephalosporin Allergy Can Be Safely Given Cefazolin While Undergoing Joint Arthroplasty.
Academic Article
Overview
abstract
BACKGROUND: Cefazolin, a first-generation cephalosporin, is the standard antibiotic for perioperative prophylaxis in patients undergoing hip or knee arthroplasty. Research has demonstrated significantly higher periprosthetic joint infection (PJI) rates when non-cefazolin antibiotics are used for prophylaxis. Notably, cefazolin contains an R1 side chain that has not shown cross-reactivity with other cephalosporins. However, in patients with a reported cephalosporin allergy, there is often uncertainty about the optimal antibiotic choice. This study aimed to determine the safety of perioperative cefazolin in patients with a documented cephalosporin allergy undergoing joint arthroplasty. METHODS: We reviewed the records of 1,268 patients who had a documented cephalosporin allergy and underwent total hip or knee arthroplasty at a high-volume academic center from 2016 to 2024. We compared patients who received cefazolin despite a cephalosporin allergy (n = 482) and patients who received an alternative antibiotic prophylaxis (n = 786). The primary outcome was the incidence of immunoglobulin E (IgE)-mediated allergic reactions or "severe" Type-IV delayed hypersensitivity reactions with end organ dysfunction within 72 hours postoperatively. The secondary outcomes included 90-day rates of complications including PJI, Clostridioides difficile infections, adverse events related to the antibiotic, and readmission. RESULTS: The incidence of an allergic reaction in patients with an allergy to cephalosporin who received cefazolin was 0.0% (0 of 482) compared with 0.51% (4 of 786) in patients who received an alternative antibiotic prophylaxis (p = 0.30). There were no significant differences in the rates of PJI after primary arthroplasty (0.21% compared with 0.26%; p = 0.83), C. difficile infection (0.0% compared with 0.0%), or readmission within 90 days (3.95% compared with 4.33%; p = 0.75). One patient who received cefazolin experienced mild, self-limited urethral irritation. Five patients receiving alternative antibiotics experienced antibiotic-related adverse events, including skin reactions, gastrointestinal distress, pancreatitis, and headache. CONCLUSIONS: In this cohort of patients undergoing joint arthroplasty, cefazolin administration in patients with a cephalosporin allergy was associated with a 0.0% incidence of IgE-mediated or severe Type-IV allergic reactions. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
