Cross-reactivity associated with delayed type hypersensitivity (DTH) arising from cephem antibiotics with a tetrazolyl group in the C-3 side chain was investigated by clinical testing and animal experiments.Clinical cross-reaction testing was performed with the leucocyte migration inhibition test (LMIT) with respect to sixteen patients with hypersensitivity induced by cephems with a tetrazolyl group in the C-3 side chain. The proportion of positive LMIT cross-reactions to cephems with a tetrazolyl group in the C-3 side chain was 78(25/32), to cephems without a tetrazoryl group, 5(1/22), and to penams, 0(0/12). The proportion of positives in tests performed with methyl-tetrazolethiol (MTT) and hydroxyethyl-tetrazolethiol (HTT), which essentially represent the structures of the C-3 side-chains in the allergenic drugs, was 29(4/14), while the corresponding proportion for 7-aminocephalosporanic acid (7ACA), which represents the skeleton structure of the cephem antibiotics, was 33(1/3).The animal experiments were performed with guinea pigs, with latamoxef, cefo-perazone and MTT as the sensitizing agents and testing for cross-reactivity by means of delayed type intradermal reactions as well as the LMIT. The results of intra-dermal testing and the LMIT agreed almost completely, thus providing strong support for the clinical results. Latamoxef and cefoperazone displayed the same cross-reactivity, manifesting cross-reactions with MTT, HTT and 7ACA as well as with cephems having a tetrazolyl group in the C-3 side chain. Moreover, DTH induced by MTT displayed cross-reactivity with cephems possessing tetrazolyl groups in the C-3 side chain.The above results indicate that free MTT radicals, as well as the skeleton ring structure represented by 7ACA, are strongly involved in DTH arising from cephem antibiotics with a tetrazolyl group in the C-3 side chain.
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