DOI: 10.1093/ajhp/zxag138 ISSN: 1079-2082

Cefazolin for all or just some? A review of cefazolin for surgical site infection prophylaxis in patients with β-lactam allergies

Meghan N Jeffres

Abstract

Purpose

To evaluate recent studies assessing the safety of cefazolin for surgical site infection (SSI) prophylaxis in patients with reported β-lactam allergies and to review interventions aimed at optimizing its use in this population.

Summary

Decades of clinical practice have been shaped by misleading assumptions regarding the degree of cross-reactivity between penicillins and cephalosporins. Contemporary evidence demonstrates that cefazolin, a first-generation cephalosporin with a unique R1 side chain, is not cross-reactive with penicillins and is well tolerated in patients with histories of immediate and severe delayed hypersensitivity reactions. Retrospective and prospective studies consistently report low rates of cefazolin-associated hypersensitivity reactions, including in cohorts with high-risk allergy histories. In contrast, alternative agents such as clindamycin and vancomycin are associated with higher rates of SSI and adverse effects. Institutional interventions, including educational initiatives, protocol-based antibiotic selection, and R1 side chain–based algorithms, have successfully increased cefazolin utilization without increasing the incidence of hypersensitivity events.

Conclusion

Cefazolin is a safe and effective agent for SSI prophylaxis and should be used in patients with β-lactam allergies. Overcoming persistent misconceptions and adopting evidence-based prescribing strategies can reduce unnecessary avoidance of cefazolin, decrease postoperative infection rates, and improve patient outcomes.

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