Cefazolin and the R1 Side Chain: Why Patients with a Cephalosporin Allergy Can Be Safely Given Cefazolin While...

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.

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.

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.

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.

Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.