Cross-reactivity between a penicillin and a cephalosporin with the same side chain

Background: The cross-reactivity between penicillins and cephalosporins can be influenced by different factors, which ar not all well known. The chemical structure of the side chain may contribute to the cross-reactivity. Objective: The study was carried out in allergic subjects who are selectively responsive to amoxicillin to determine allergenic cross-reactivity with a cephalosporin containing a side chain identical to that of amoxicillin, cefadroxil, and one containing a different side chain, cefamandole. Methods: Allergic subjects with a selective response to amoxicillin were chosen according to the following criteria: history of an immediate allergic reaction to amoxicillin, negative skin test responses to benzylpenicilloyl and minor determinant mixture of benzylpenicillin, negative RAST response to benzylpenicilloyl, and good tolerance to benzylpenicillin and phenoxymethyl penicillin challenges. In addition, subjects had to have a positive skin test response to amoxicillin and/or positive RAST response to amoxicilloyl or, if these test results were negative, a positive challenge test response to amoxicillin. In vivo cross-reactivity to cefadroxil was assessed by giving oral cefadroxil at increasing doses form 5 to 500 mg. In vitro cross-reactivity was determined by RAST inhibition studies with amoxicilloyl RAST disks and the following monomeric conjugates in the fluid phase: amoxicillin-butylamine, cefadroxil-butylamine, and the side chain para-hydroxy-phenylglycine. Tolerance to cefamandole was determined by giving 100 mg and then 500 mg parenterally. Results: Twenty-one patients with a selective response to amoxicillin were included in the study. Eight subjects (38%) had a positive response to cefadroxil, and none reacted to cefamandole. In vitro RAST inhibition studies indicated that cefadroxil-butylamine monomers cross-reacted with amoxicillin butylamine and the side chain contributed relevantly to the inhibition. Conclusions: These results indicate that the percentage of cross-reactivity between penicillins and cephalosporins with an identical side chain is high and that this critical part of the molecule seems to be an important contributor to these results. The value is higher than previously reported data from similar studies of non-side-chain-related cephalosporins.