Did you know the literature describing the cross-reactivity between cephalosporins and penicillins is 30-40 years old? It sort of takes the “modern” out of “modern medicine.”
At any rate, this is a literature review that aims to update the classical teaching that cross-reactivity between cephalosporins and PCN is ~10%. They identified 406 articles on the topic and distilled it down to 27 respectable articles for inclusion in summary. They rate the quality of the articles, and, unfortunately, find only a few good or outstanding articles and a preponderance of adequate evidence.
But, essentially, what they find is the cross-reactivity boils down to the presence of a shared R1 side chain present on first-generation and some second-generation cephalosporins. Specific first-generation cephalosporins, such as cefadroxil (Duracef), were seen to have up to 28% cross-reactivity in some series, though the typical rate was lower, down to 0.11% with cefazolin (Ancef). The largest meta-analyses estimated the true cross-reactivity at ~1% rather than 10%, with most of these occurring with first-generation cephalosporins.
In summary – 3rd-generation and greater cephalosporins with disimilar R1 side chains can probably be used in appropriate clinical situations despite a PCN allergy without incidence of allergy greater than in those patients who do not have a documented PCN allergy.
“The use of cephalosporins in penicillin-allergic patients: A literature review.”
It's important to note that of the population that claims a penicillin allergy, only about 10-20% of those patients are truly allergic based on skin testing.
Also, not all allergic reactions are created equal. In those who are truly penicillin allergic, most will have mild reactions (rashes), and very few (<0.1%) will have life-threatening reactions (IgE-mediated anaphylaxis).
As you point out, given the very low incidence of cross-sensitivity, the fact that 80-90% of patients don't actually have a penicillin allergy, and the >99% chance that an actual cross-sensitivity will not result in a life-threatening reaction, we should be less worried about using cephalosporins in penicillin-allergic patients!
(More info at http://www.ncbi.nlm.nih.gov/pubmed/18044279)
Great point – although, I think a lot of the articles included in the cephalosporin/PCN allergy analysis included confirmed skin-test allergy to PCN. And, yes, it's one thing to have a 0.1% incidence of allergic reaction, and another matter entirely whether a significant portion of those allergies are anaphylactoid.