Which cephalosporin is least likely to cross-react with amoxicillin due to a dissimilar side chain?

• A. Cefadroxil
• B. Cephalexin
• C. Cefaclor
• D. Cefdinir

Answer: (D)

Cross-reactivity between penicillins and cephalosporins mainly depends on how similar their side chains are. If a cephalosporin has a side chain that is dissimilar to the penicillin’s side chain, the immune system is less likely to recognize it as the same allergen. Cefdinir has a side chain that is more different from amoxicillin’s side chain than the others listed, making it the least likely to cross-react. The other cephalosporins share side-chain features that are more reminiscent of penicillin structures, which can elevate the chance of cross-reactivity. In clinical practice, consider this concept when selecting a cephalosporin for someone with a penicillin allergy, and monitor as needed.