UMEM Educational Pearls

Category: Pharmacology & Therapeutics

Title: Tolerability of penicillins in cephalosporin-allergic patients

Keywords: penicillin, cross-reactivity, cephalosporin, IgE, allergy (PubMed Search)

Posted: 10/29/2012 by Bryan Hayes, PharmD (Emailed: 11/3/2012) (Updated: 11/3/2012)
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It seems we've finally put to bed the myth that 10% of penicillin-allergic patients will also react to cephalosporins. Dr. Campagna, et al. recently published a review article concluding that the true cross-reactivity is negligible except when side-chains are similar [PMID 21742459]. 

This topic was also the subject of a recent post on the Academic Life in EM blog (

But what about the reverse question? Can I give a penicillin to a cephalosporin-allergic patient?

Dr. Romano's group tested 98 patients with skin-test postitive cepahlosprin allergy (mostly IgE -mediated anaphylaxis). Patients were then skin tested for penicillin allergy. Those testing negative were challenged with a penicillin.

  • 25% of patients reacted to the penicillin

  • Similar side-chain was a strong predictor of cross-reactivity

​A Letter to the Editor response to this study pointed out that the authors used a smaller-than-standard size threshold for a positive response to the penicllin AND used a higher-than-standard dose of amoxicillin for testing. In light of this, the rate of subjects with cephalosporin allergy who do not have a history of penicillin allergy but with true IgE-mediated allergy to penicillin might be much closer to 5%.

Bottom line: The cross-reactivity of penicillins in cephalosporin-allergic patients is somewhere between 5-25%.


Romano A, et al. IgE-mediated hypersensitivity to cephalosporings: cross-reactivity and tolerability of penicillins, monobactams, and carbapenems. J Allergy Clin Immunol 2010;126(5):994-9.

Macy E. Penicillin allergy might not be very common in subjects with cephalosporin allergy. J Allergy Clin Immunol 2011;127(6):1638-9.

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