Immediate hypersensitivity to cephalosporins.

Cephalosporins are the second most important beta -lactams after penicillins for treating infectious diseases. Like the latter, they may cause allergic reactions, especially IgE-mediated ones. Many of these manifestations, such as urticaria and exanthema, are cutaneous, but anaphylactic reactions have also been reported. In a study of fatal anaphylaxis in the UK between 1992 and 1997, six of the 12, fatal reactions attributed to antibiotics followed the first dose of a course of cephalosporin. The frequency of skin reactions in patients treated with cephalosporins ranges from 1 (cefuroxime) to 3% (ceftriaxone). The incidence of the reactions to cephalosporins does not seem to be less than that to penicillins, but immediate allergic reactions to cephalosporins and the nature of their allergenic determinants have been far less studied. There are few useful data regarding several fundamental and applied aspects of cephalosporin immunochemistry, such as the characterization of their allergenic determinants, the role of side-chain structures in allergenicity, and allergenic cross-reactivity with other beta-lactams. However, we know that cephalosporins share the four-membered beta-lactam ring with penicillins, but differ from the latter in that the five-membered thiazolidine ring of penicillin is replaced by a six-membered dihydrothiazine one. Other differences between the two regard their side-chain structures and the chemistry of their degradation and transformation. Under physiological conditions, the cephalosporin -lactam ring opens and with its carbonyl moiety binds a protein, forming the cephalosporoyl determinant , which tends to fragment extensively. Side-chain structures usually survive such fragmentation and may be responsible for cross-reactivity among beta-lactams, including other cephalosporins, or selective sensitization. In vitro studies have demonstrated IgE antibody reactivity with both ends of the cephalosporin molecule, i.e. the side-chain group (R1 substituent) and the ring structures with the attached R2 group. The production of hybridomae has shown that, in addition to common determinants, cephalosporins can generate unique structures capable of inducing a specific immunologic response not cross-reacting with classic structures. Thus, allergic reactions to cephalosporins may occur because of sensitization to determinants shared with penicillins or to unique cephalosporin haptens. It already seems clear that, as with penicillins, cephalosporins as allergens cannot simply be considered as a group of compounds with a common allergenic determinant structure.