Understanding Penicillin Allergy, Cross-reactivity, and Antibiotic Selection in the Preoperative Setting

J Am Acad Orthop Surg. 2022 Jan 1;30(1):e1-e5. doi: 10.5435/JAAOS-D-21-00422.


Penicillin allergies are reported by 8% to 15% of the US population, but up to 95% of these allergies do not correspond to a true allergy when tested. Recent studies have demonstrated that having a penicillin allergy label (PAL) results in a 50% increased odds of surgical site infection among patients reporting a penicillin allergy entirely attributable to the use of a beta-lactam alternative antibiotic (primarily clindamycin or vancomycin). This study provides a review of the prevalence of PAL, the cross-reactivity with cefazolin, immunogenic components of cefazolin and penicillin, and current guidelines for preoperative antibiotic selection in patients with PALs. On understanding these principles, a new set of guidelines and a risk stratification tool are proposed for assessing allergies and determining appropriate antibiotic choice, dosage, and timing in the orthopaedic preoperative setting.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents* / adverse effects
  • Antibiotic Prophylaxis
  • Drug Hypersensitivity* / diagnosis
  • Drug Hypersensitivity* / epidemiology
  • Drug Hypersensitivity* / etiology
  • Humans
  • Penicillins / adverse effects
  • Retrospective Studies


  • Anti-Bacterial Agents
  • Penicillins