Evaluating Immediate Reactions to Cephalosporins: Time Is of the Essence

J Allergy Clin Immunol Pract. 2021 Apr;9(4):1648-1657.e1. doi: 10.1016/j.jaip.2020.11.032. Epub 2020 Nov 27.


Background: Few studies have assessed the diagnostic value of cephalosporin skin tests in patients with immediate reactions to these β-lactams.

Objective: To evaluate the usefulness of skin tests and challenges in assessing such subjects.

Methods: We conducted a prospective study of 236 consecutive subjects who had suffered 249 immediate reactions (mostly anaphylaxis) to cephalosporins. Skin tests were performed with penicillin reagents and suspected cephalosporins. Serum specific IgE assays (ImmunoCAP) were also carried out for penicillins and cefaclor. Subjects with negative results underwent challenges with the suspected cephalosporins; patients with negative results who had been assessed more than 6 months after their reactions were reevaluated.

Results: In the first allergy workup, an IgE-mediated hypersensitivity to cephalosporins was diagnosed in 164 (69.5%) of the 236 patients on the basis of skin test (162 patients) or cefaclor ImmunoCAP positivity (2 patients). Of the 72 patients with negative results, 55 underwent cephalosporin challenges; 3 reacted. Twenty subjects were reevaluated after cephalosporin negative challenges, with a conversion to cephalosporin skin test positivity occurring in 5 of the 6 subjects who had had anaphylactic reactions and in none of the remaining 14 subjects with other reactions. Overall, an immediate hypersensitivity to cephalosporins was diagnosed in 172 patients (of whom it was diagnosed in 5 after retesting).

Conclusions: Most immediate reactions to cephalosporins are IgE-mediated. Cephalosporin skin testing is a useful tool for evaluating these reactions. IgE-mediated cephalosporin hypersensitivity may be a transient condition; therefore, allergy examinations should be repeated in patients with negative results who experienced anaphylaxis more than 6 months before the allergy workup, including challenges.

Keywords: Cefaclor; Ceftriaxone; Cephalosporins; Challenges; Penicillins; Skin tests; Specific IgE; β-Lactams.

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Cephalosporins / adverse effects
  • Cross Reactions
  • Drug Hypersensitivity* / diagnosis
  • Drug Hypersensitivity* / epidemiology
  • Humans
  • Hypersensitivity, Immediate*
  • Immunoglobulin E
  • Penicillins
  • Prospective Studies
  • Skin Tests


  • Anti-Bacterial Agents
  • Cephalosporins
  • Penicillins
  • Immunoglobulin E