Safety of Perioperative Cefazolin in Penicillin-Anaphylactic Patients for Total Hip and Knee Arthroplasty.

Abstract

Cefazolin, a first-generation cephalosporin, is the preferred antibiotic for prophylaxis in elective primary total hip and knee arthroplasties (THAs and TKAs). While most of its chemical structure differs from penicillin (PCN), its shared beta-lactam ring has historically raised concerns about cross-reactivity in patients who have with reported PCN allergies. However, studies suggest that patients who report a PCN allergy have a 50% increased odds of surgical site infection, often due to receiving second-line perioperative antibiotics. In 2022, our institution implemented a protocol allowing cefazolin administration for all patients, including those who have PCN allergies, except in cases of documented severe non-IgE-mediated reactions. This study analyzed the incidence of anaphylaxis to cefazolin in patients who have documented anaphylactic PCN allergies undergoing primary THA or TKA. We conducted a retrospective cross-sectional study of 8,456 patients who underwent THA or TKA at a tertiary academic center between 2008 and 2024. Patients were grouped as anaphylactic PCN allergic, nonanaphylactic PCN allergic, and a non-PCN allergy control. Along with perioperative antibiotic use, epinephrine (EPI) administration and rapid response team (RRT) activation were recorded as markers of anaphylaxis. Statistical analysis included logistic regression, Chi-square, and Fisher's exact tests. Among 214 patients who had documented PCN anaphylaxis who received cefazolin, only one patient experienced RRT or EPI, which was not statistically significant. In all patients and the subgroup without documented PCN allergies, vancomycin use was significantly associated with RRT or EPI in these groups, with odds ratios of 7.2 (95% CI [confidence interval]: 4.4 to 11.7) and 11.6 (95% CI: 6.9 to 19.7), respectively. Cefazolin administration did not significantly increase the risk of anaphylaxis or clinical instability in patients who had documented PCN anaphylaxis. These findings support the safety of cefazolin in anaphylactic PCN-allergic patients, potentially reducing the reliance on less effective second-line antibiotics.