Pearl: For patients with a true penicillin allergy, especially a Type I (IgE) reaction, increased cross-reactivity with first generation cephalosporins is real, but with third generation is not.

Background: Some of us were taught a cross-reactivity rate between PCN allergies and cephalosporins as high as 10%. This appears to have emerged from a few low-quality studies in the ’50s and ’60s. On the flip side, some of us listening to FOAM have likely mentally combined posts about the low rate of “real” allergies among patients who claim them with posts on the low-rate of cross-reactivity and produced the logical fallacy that all cross-reactivity is made up.

Some factoids:

  • First generation cephalosporins were actually made by modifying a penicillin side-chain, resulting in true contamination of the medicine with residual, unmodified penicillin.
  • The allergic reaction to penicillins and cephalosporins is due to a side chain and not the beta-lactam group, despite us calling it a beta-lactam allergy at times.
  • Each penicillin, ampicillin and amoxicillin has first and second generation counterparts with some it shares nearly identical side chains. These tend to have higher rates of cross-reactivity
  • Rates of true allergy amoung patients stating they have a PCN allergy have been repeatedly found to be under 25%
  • The OR of cross-reactivity from a PCN allergy to a first-gen cephalosporin is ~4. This is not negligible. It drops to nearly 1 for second generation and is 1 by third generation. First generation cephalosporins should probably be avoided in truly allergic patients, particularly anaphylactic ones.

Bonus Pearl: “Ondine’s Curse” refers to Central Hypoventillation Syndrome and is so named after a 19th century of a water nymph who made a pact that if her lover proved to be unfaithful, as she was warned, he would lose the ability to breathe without her. https://en.wikipedia.org/wiki/Central_hypoventilation_syndrome

Major Source:

Campagna JD1Bond MCSchabelman EHayes BD. The use of cephalosporins in penicillin-allergic patients: a literature review. J Emerg Med. 2012 May;42(5):612-20.

doi: 10.1016/j.jemermed.2011.05.035. Epub 2011 Jul 13.