Which cephalosporin has the highest likelihood of cross-reacting with amoxicillin or ampicillin due to similar side chains?

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

Answer: (D)

Understanding why this cephalosporin is the most likely to cross-react with amoxicillin or ampicillin comes down to side-chain similarity. Amoxicillin and ampicillin share a specific amino-phenylacetic side chain. Cephalosporins that have a matching or very similar R1 side chain to those aminopenicillins are more likely to trigger a cross-reactive immune response. Among the options, the cephalosporin with the side chain most closely resembling that amino-phenylacetic group is cefdinir, so it carries the highest chance of cross-reacting with penicillins. The other cephalosporins listed have different R1 side chains, making cross-reactivity less likely.

In general, cross-reactivity is relatively uncommon but is influenced more by side-chain similarity than by the cephalosporin’s generation.