Immunoglobulin E binding determinants on β-lactam drugs

Abstract

Allergies to penicillins and cephalosporins remain an important clinical problem, but structural and immunochemical knowledge of the allergenic structures involved has tended to lag behind the heavy usage, consequent adverse reactions and introduction of new therapeutic members of these two families of antibiotics. Evidence of the increasing incidence of reactions to cephalosporins and to "minor" determinants of the beta-lactams is accumulating. Also, although numerous reports detail unique allergic recognitions of individual members of the two families, particularly the cephalosporins, information remains predominantly clinical. The present review summarizes the most recent advances in studies of structural aspects of beta-lactams as allergens. For the cephalosporins, a pyrazinone allergenic degradation product of cefaclor and cephalexin has been identified and characterized. The widely used cephalosporin cephalothin was shown to cross-react allergenically with benzylpenicillin and the common cross-reacting structure was identified. The fine structural features on the amoxicillin molecule recognized by antibodies that distinguish "major" and "minor" determinants were identified, and steric factors were used to explain antibody recognition of the amoxicillin determinants. A recent study elucidated the molecular basis of some cases of the multiple drug allergy syndrome and its relationship to beta-lactam allergy. Findings of the type described in the present review provide fundamental insights into the nature and size of antigenic determinants on "small" molecules such as drugs and other chemicals. At the clinical level, such structure/activity findings have implications for our understanding of drug allergenic cross-reactions, for selection for therapy of an appropriate member from a family of structurally related drugs and, ultimately, for desensitization of drug-allergic patients.