Diagnostic Approach of Hypersensitivity Reactions to Cefazolin in a Large Prospective Cohort

J Allergy Clin Immunol Pract. 2021 Dec;9(12):4421-4430.e4. doi: 10.1016/j.jaip.2021.08.017. Epub 2021 Aug 28.


Background: Cefazolin is a common trigger of perioperative anaphylaxis. The diagnostic approach is controversial because the optimal concentration for skin testing is uncertain, drug provocation tests (DPTs) are contraindicated in severe reactions, and in vitro tests are not thoroughly validated.

Objective: We aimed to characterize a large number of patients reporting cefazolin allergic reactions and to analyze the diagnostic role of in vivo and in vitro tests.

Methods: We prospectively evaluated patients with suspicion for allergic reactions to cefazolin by clinical history, skin tests (STs), and, if negative, DPT. In a subgroup of patients, basophil activation test (BAT) and radioallergosorbent test were done before allergologic workup was performed and the final diagnosis was achieved.

Results: We evaluated 184 patients, 76 of whom were confirmed as allergic (41.3%), 90 were nonallergic (48.9%), and 18 were nonconfirmed (9.8%). All patients reporting anaphylactic shock and most reporting anaphylaxis were confirmed to be allergic (P < .001). Forty allergic patients (52.6%) were confirmed by STs, 22 by DPT (28.9%), and 14 by clinical history (18.4%). All subjects manifesting exanthemas and pruritus were nonallergic. The BAT sensitivity was 66.7% when CD63 and CD203c were combined as activation markers. Six of 8 patients with negative STs and positive DPT had a positive BAT.

Conclusions: Patients allergic to cefazolin often reported severe immediate-type reactions. Skin tests enabled a diagnosis in half of patients when using cefazolin at 20 mg/mL. Unfortunately, DPT could not be performed in all patients owing to reaction severity, which makes BAT a promising diagnostic tool. Further research is needed to clarify the underlying mechanisms, especially in severe reactions.

Keywords: Anaphylaxis; Basophil activation test; Cefazolin; In vitro test; In vivo diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basophil Degranulation Test
  • Cefazolin
  • Drug Hypersensitivity* / diagnosis
  • Drug Hypersensitivity* / epidemiology
  • Humans
  • Hypersensitivity, Immediate* / diagnosis
  • Prospective Studies
  • Skin Tests


  • Cefazolin