Cross-Reactivity and Tolerability of Cephalosporins in Patients with IgE-Mediated Hypersensitivity to Penicillins

J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1662-1672. doi: 10.1016/j.jaip.2018.01.020. Epub 2018 Feb 3.


Background: Studies performed since 1990 on samples of at least 30 subjects with a documented IgE-mediated hypersensitivity to penicillins have found a rate of positive responses to allergy tests with cephalosporins ranging from 0% to 27%.

Objective: We sought to assess the cross-reactivity with cephalosporins and evaluate the possibility of using cephalosporins in penicillin-allergic subjects.

Methods: We conducted a prospective study of 252 consecutive subjects who had suffered 319 immediate reactions (mostly anaphylaxis) to penicillins and had positive skin tests to at least 1 penicillin reagent. All patients underwent serum specific IgE assays for cefaclor, as well as skin tests with 3 aminocephalosporins (cephalexin, cefaclor, and cefadroxil), cefamandole, cefuroxime, ceftazidime, ceftriaxone, cefotaxime, and cefepime. Patients with negative results for the last 5 cephalosporins were challenged with cefuroxime axetil and ceftriaxone; those with negative results for aminocephalosporins were also challenged with cefaclor and cefadroxil.

Results: Ninety-nine participants (39.3%) had positive allergy tests for cephalosporins. Specifically, 95 (37.7%) were positive to aminocephalosporins and/or cefamandole, which share similar or identical side chains with penicillins. All 244 subjects who underwent challenges with cefuroxime axetil and ceftriaxone tolerated them. Of the 170 patients who underwent aminocephalosporin challenges, 3 reacted to cefaclor and 4 to cefadroxil.

Conclusions: Cross-reactivity between penicillins and cephalosporins seems to be mainly related to side chain similarity or identity. Subjects with an IgE-mediated hypersensitivity to penicillins could be treated with cephalosporins such as cefuroxime and ceftriaxone that have side-chain determinants different from those of penicillins and are negative in pretreatment skin testing.

Keywords: Cephalosporins; Challenges; Cross-reactivity; Immediate reactions; Penicillins; Skin tests; Tolerability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / immunology*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / immunology*
  • Cephalosporins / chemistry
  • Cephalosporins / immunology*
  • Cross Reactions
  • Drug Hypersensitivity / immunology*
  • Drug Tolerance
  • Female
  • Humans
  • Immunoglobulin E / metabolism
  • Male
  • Middle Aged
  • Molecular Mimicry
  • Penicillins / chemistry
  • Penicillins / immunology*
  • Prospective Studies
  • Serologic Tests
  • Skin Tests
  • Structure-Activity Relationship


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