Comparison of immediate hypersensitivity reactions to preoperative antibiotics in patients labeled as penicillin allergic

Surgery. 2021 Sep;170(3):777-782. doi: 10.1016/j.surg.2021.02.063. Epub 2021 Apr 8.


Background: Cefazolin is routinely recommended as the first-line agent for surgical antibiotic prophylaxis because it prevents more surgical site infections than second-line antibiotics. Clinicians often avoid administering cefazolin to patients who are labeled as penicillin allergic due to concerns of cross-reactivity. The aim of this study was to compare the incidence of hypersensitivity reactions between cefazolin and the second-line antibiotics vancomycin and clindamycin.

Methods: This retrospective study included patients who were labeled as penicillin allergic and received either cefazolin, clindamycin, or vancomycin as preoperative antibiotics. The primary outcome was intraoperative hypersensitivity reactions.

Results: A total of 734 surgical procedures in 690 patients were included. Fifteen immediate hypersensitivity reactions were identified. Probable hypersensitivity reactions occurred in 3 (0.9%) patients in the cefazolin group, 4 (1.4%) in the clindamycin group, and 1 (1.1%) in the vancomycin group. Seven of 8 patients reported allergies to additional medications beyond penicillin. There were seven cases of possible hypersensitivity reactions, 3 (0.9%) in the cefazolin group, 1 (1.1%) in the vancomycin group, and 3 (1.0%) in the clindamycin group.

Conclusion: Our data suggest that perioperative hypersensitivity reactions are uncommon in patients labeled as penicillin allergic. The frequency of immediate hypersensitivity reactions was not different between patients receiving cefazolin, clindamycin, or vancomycin. Avoiding cefazolin in patients labeled as penicillin allergic may not be warranted.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Antibiotic Prophylaxis / adverse effects*
  • Antibiotic Prophylaxis / methods
  • Cefazolin / adverse effects*
  • Cefazolin / therapeutic use
  • Clindamycin / adverse effects*
  • Clindamycin / therapeutic use
  • Drug Hypersensitivity / etiology*
  • Female
  • Humans
  • Hypersensitivity, Immediate / chemically induced*
  • Intraoperative Period
  • Male
  • Middle Aged
  • Penicillins / adverse effects*
  • Retrospective Studies
  • Surgical Procedures, Operative / adverse effects
  • Surgical Procedures, Operative / methods
  • Vancomycin / adverse effects*
  • Vancomycin / therapeutic use


  • Anti-Bacterial Agents
  • Penicillins
  • Clindamycin
  • Vancomycin
  • Cefazolin