Cefazolin Proven Safe for Beta-Lactam-Allergic Patients in Joint Surgery: Study

Cefazolin continues to be the drug of preference for prevention of SSI in total joint arthroplasty with its spectrum efficacy and advantageous safety profile. Yet, patients with known beta-lactam allergy are treated with second-line drugs such as vancomycin or clindamycin that may be less effective and pose an increased risk of SSI. In the past, penicillin-cephalosporin cross-reactivity deterred cefazolin administration to this subgroup, but current data indicate that the true risk, particularly with cefazolin, is significantly lower than previously anticipated.

Researchers performed a retrospective analysis of 521 elective orthopedic procedures in one institution after the introduction of the new antibiotic regime. Included were 209 patients with a history of major beta-lactam allergy. The main aim was to monitor for immediate hypersensitivity reactions (HSRs) following the administration of cefazolin. Reactions were classified as probable or possible using intraoperative findings and response to treatment, including skin effects, hemodynamic instability, or drug cessation.

Key Findings

• Number of patients examined: 521

• Severe beta-lactam allergy history patients: 209

• Possible cefazolin hypersensitivity reactions: 0

• Potential intraoperative HSRs: 24 (5%)

• Patients tolerated further doses of cefazolin but not cefazolin: 14

• Patients who needed epinephrine for the reaction: 0

• Patients labeled as cefazolin allergic postoperatively: 0

The lack of likely hypersensitivity reactions, even among high-risk allergies, affirms cefazolin's safety. Of concern, however, was that no patients had severe allergic reactions, underwent emergency measures such as epinephrine, or needed to be excluded from future cefazolin treatment.

Cefazolin is safe to be given for SSI prophylaxis in patients with a history of reported allergy to beta-lactams, even those with a history of severe allergy, if they do not have a documented cefazolin allergy. The findings are supportive of the continued use of cefazolin as the orthopedic surgery prophylactic standard, promoting a trend toward avoiding redundant substitution with second-tier antibiotics. This not only improves patient safety but also supports antimicrobial stewardship initiatives within surgical practice.

Reference:

Clarke, Z., Koonce, R., Dayton, M. R., Hogan, C., & Jeffres, M. (2025). Safety of administering cefazolin in beta-lactam allergic patients undergoing elective orthopaedic procedures. The Journal of Arthroplasty. https://doi.org/10.1016/j.arth.2025.05.057