Cross-reactivity and tolerability of aztreonam and cephalosporins in subjects with a T cell-mediated hypersensitivity to penicillins

J Allergy Clin Immunol. 2016 Jul;138(1):179-186. doi: 10.1016/j.jaci.2016.01.025. Epub 2016 Mar 23.


Background: The few studies performed in adults with T cell-mediated hypersensitivity to penicillins have found a rate of cross-reactivity with cephalosporins ranging from 2.8% to 31.2% and an absence of cross-reactivity with aztreonam.

Objective: We sought to evaluate the possibility of using cephalosporins and aztreonam in subjects with documented delayed hypersensitivity to penicillins who especially require them.

Methods: We conducted a prospective study of 214 consecutive subjects who had 307 nonimmediate reactions to penicillins (almost exclusively aminopenicillins) and had positive patch test and/or delayed-reading skin test responses to at least 1 penicillin reagent. To assess cross-reactivity with cephalosporins and aztreonam and the tolerability of such alternative β-lactams, all subjects underwent skin tests with cephalexin, cefaclor, cefadroxil, cefuroxime, ceftriaxone, and aztreonam. Subjects with negative responses were challenged with the alternative β-lactams concerned.

Results: All subjects had negative skin test results to cefuroxime, ceftriaxone, and aztreonam and tolerated challenges. Forty (18.7%) of the 214 subjects had positive skin test responses to at least 1 aminocephalosporin. Of the 174 subjects with negative responses, 170 underwent challenges; 1 reacted to cefaclor.

Conclusions: These data demonstrate a rate of cross-reactivity between aminopenicillins and aminocephalosporins (ie, cephalexin, cefaclor, and cefadroxil) of around 20%, as well as the absence of cross-reactivity between penicillins and cefuroxime, ceftriaxone, and aztreonam in all subjects with T cell-mediated hypersensitivity to penicillins, almost exclusively aminopenicillins. Therefore these subjects could be treated with cefuroxime, ceftriaxone, and aztreonam. In those who especially require cephalosporin or aztreonam treatment, however, we recommend pretreatment skin tests because negative responses indicate tolerability.

Keywords: Aztreonam; cephalosporins; challenges; cross-reactivity; nonimmediate reactions; penicillins; skin tests; tolerability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aztreonam* / adverse effects
  • Cephalosporins* / adverse effects
  • Cross Reactions / immunology*
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / immunology*
  • Female
  • Humans
  • Hypersensitivity, Delayed / diagnosis*
  • Hypersensitivity, Delayed / immunology*
  • Immune Tolerance*
  • Immunoglobulin E / immunology
  • Male
  • Middle Aged
  • Patch Tests
  • Penicillins / adverse effects*
  • Phenotype
  • Skin Tests
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Young Adult


  • Cephalosporins
  • Penicillins
  • Immunoglobulin E
  • Aztreonam