CROSS-REACTIVITY BETWEEN A PENICILLIN AND A CEPHALOSPORIN WITH THE SAME SIDE-CHAIN

Background: The cross-reactivity between penicillins and cephalosporin s 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 identica l to that of amoxicillin, cefadroxil, and one containing a different s ide chain, cefamandole. Methods: Allergic subjects with a selective re sponse to amoxicillin were chosen according to the following criteria: history of an immediate allergic reaction to amoxicillin, negative sk in test responses to benzylpenicilloyl and minor determinant mixture o f benzylpenicillin, negative RAST response to benzylpenicilloyl, and g ood tolerance to benzylpenicillin and phenoxymethyl penicillin challen ges. In addition, subjects had to have a positive skin test response t o amoxicillin and/or positive RAST response to amoxicilloyl or, if the se test results were negative, a positive challenge test response to a moxicillin. In vivo cross-reactivity to cefadroxil was assessed by giv ing oral cefadroxil at increasing doses form 5 to 500 mg. In vitro cro ss-reactivity was determined by RAST inhibition studies with amoxicill oyl RAST disks and the following monomeric conjugates in the fluid pha se: 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 patie nts with a selective response to amoxicillin were included in the stud y. Eight subjects (38%) had a positive response to cefadroxil, and non e reacted to cefamandole. In vitro RAST inhibition studies indicated t hat cefadroxil-butylamine monomers cross-reacted with amoxicillin buty lamine and the side chain contributed relevantly to the inhibition. Co nclusions: These results indicate that the percentage of cross-reactiv ity between penicillins and cephalosporins with an identical side chai n is high and that this critical part of the molecule seems to be an i mportant contributor to these results. The value is higher than previo usly reported data from similar studies of non-side-chain-related ceph alosporins.