Beta-lactam hypersensitivity and cross-reactivity

J Pharm Pract. 2014 Dec;27(6):530-44. doi: 10.1177/0897190014546109. Epub 2014 Aug 14.


Penicillin is the most frequently reported cause of drug allergy, and cross-reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This review evaluates the available data on immunoglobulin E-mediated penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem, and monobactam antibiotics. A MEDLINE search was conducted from 1950 to October 2013, and selected references from review articles were also evaluated. There is a wide variety in reported incidences of cross-reactivity between penicillins and cephalosporins or carbapenems, with early retrospective studies suggesting up to 41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of monobactam antibiotics is frequently employed in the case of a penicillin allergy, as prescribers believe that there is no cross-reactivity between the 2 drug classes. More recent prospective studies suggest that the rates of cross-reactivity with cephalosporins and carbapenems are <5% and <1%, respectively. Similarities in penicillin and cephalosporin side chains may play a role in cross-reactivity between these classes. Cross-reactivity with monobactams is essentially negligible; however, there are some clinical data to support an interaction between ceftazidime and aztreonam, due to the similarity of their side chains. The data reviewed suggest that avoidance of other beta-lactams in patients with type 1 hypersensitivity to penicillins should be reconsidered.

Keywords: beta-lactam; cross-reactivity; hypersensitivity; penicillin.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / adverse effects*
  • Carbapenems / adverse effects*
  • Cephalosporins / adverse effects*
  • Cross Reactions
  • Drug Hypersensitivity*
  • Humans
  • Monobactams / adverse effects*
  • Penicillins / adverse effects*


  • Anti-Bacterial Agents
  • Carbapenems
  • Cephalosporins
  • Monobactams
  • Penicillins