Penicillins (PCN) and cephalosporins were produced with the same fungi during synthesis. This increased the rate of cross contamination especially prior to 1980. Although the allergy was though to be due to the similarities in the beta-lactam ring it is more probably caused due to manufacturing contamination although there is cross reactivity risk based on side chain similarity. 1st and 2nd generation penicillins share the same R-1 side chain. However, a current review of the literature demonstrates that the 10% or greater allergy may be exaggerated.
- 1st generation cephalosporins: cefadroxil, cefatrizine, cephalexin, cephradine
- 2nd generation cephalosporins: cefaclor, cefprozil
Campagna Review Article
- Overall cross-reactivity rate between cephalosporins and penicillins in patients reporting a penicillin allergy = 1%. 
- Overall cross-reactivity rate in patients with a confirmed penicillin allergy = 2.5%.
- Cross-reactivity between penicillins and 1st and 2nd generation cephalosporins is possible.
- Cross-reactivity between penicillins and ALL 3rd and 4th generation cephalosporins is negligible.
- If a patient has an allergy to amoxicillin or ampicillin, avoid cefadroxil, cefaclor, cefatrizine, cefprozil, cephalexin, and cephradine.
- UIC Pharmacology on Penicillin Cross Reactivity https://www.uic.edu/pharmacy/services/di/crossens.htm
- Campagna JD, Bond MC, Schabelman E, Hayes BD. The use of cephalosporins in penicillin-allergic patients: A literature review. J Emerg Med. 2012;42(5):612-20