Background Cefazolin, a first-generation cephalosporin, is the recommended prophylactic antibiotic for hip and knee arthroplasty. Literature demonstrates higher prosthetic joint infection (PJI) rates with alternative antibiotics. Cefazolin's unique R1 side-chain, the antigenic determinant of cephalosporins, has not demonstrated cross-reactivity with other cephalosporins. Despite this, a documented cephalosporin allergy often leads to use of alternative antibiotics, potentially increasing PJI risk. This study aimed to evaluate the safety of cefazolin administration in arthroplasty patients with cephalosporin allergy. Methods We performed a retrospective cohort study of all patients with a reported allergy to cephalosporins. Patients receiving cefazolin were compared to those receiving alternative antibiotics. The primary outcome was incidence of IgE-mediated or severe Type-IV hypersensitivity reactions within 72-hours postoperatively. Secondary outcomes included 90-day rates of PJI, C. difficile infection, adverse events, and readmissions. Statistical analysis included chi-square or Fisher exact tests for categorical variables, and t-tests or Mann-Whitney U tests for continuous variables. Results 89,993 hip and knee arthroplasty patients from 2016–2024 were identified from our institutional database. Of these, 1,267 had a documented cephalosporin allergy. The incidence of hypersensitivity reactions in cephalosporin-allergic patients who received cefazolin was 0.0% (0/481), versus 0.51% (4/786) in those receiving alternative antibiotics (p=0.12). All reactions required supportive treatment with IV fluids, corticosteroids, and antihistamines. There were no differences in PJI (0.23% vs. 0.30%; p=0.83), C. difficile infection (0% vs. 0%), and 90-day readmissions (3.95% vs. 4.34%; p=0.75). One adverse event (urethral irritation) was reported with cefazolin. Four adverse events occurred in the alternative group (cutaneous reaction, gastrointestinal symptoms, pancreatitis, headache). Conclusion This is the first study to evaluate prophylactic cefazolin in hip and knee arthroplasty patients with a documented cephalosporin allergy and resulted in no IgE-mediated or severe Type IV hypersensitivity reactions. These findings support the administration of cefazolin in most arthroplasty patients reporting cephalosporin allergy.
Jolissaint et al. (Thu,) studied this question.