STUDIES OF BETA-LACTAM ANTIBIOTIC ALLERGY

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IgE antibody mediated reactions to beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, and monobactams) frequently complicate therapy with these agents and impose a serious limitation on their use. Skin tests and in vitro specific IgE assays that can accurately identify penicillin allergic patients have been developed, but several important issues pertaining to penicillin allergy remain unresolved. The structurally similar beta-lactam antibiotics, now more widely used than benzylpenicillin G, impose new problems for diagnosis and management of allergic reactions. The experiments described in this proposal address fundamental issues in three related areas of human beta-lactam drug allergy: the diagnosis and management of penicillin allergy; the in vitro detection and characterization of IgE to cephalosporins; and the process of dehaptentation of proteins substituted with beta-lactam antibiotic determinants. In first group of experiments, new in vitro methods for the detection of IgE t penicillin and conventional penicillin skin tests will be used to clarify controversial issues pertaining to the accurate diagnosis of penicillin allergy. Competing possible explanations for acute beta-lactam drug desensitization will be investigated. Resensitization of patients treated with a beta-lactam drug will be explored. The second group of experiments will study IgE to cephalosporin determinants and determinants formed from other beta-lactam drugs using new in vitro assay methods. Crossreactivities among cephalosporin and other beta-lactam determinants will be measured. The third group of experiments will characterize dehaptenation of human proteins. Recent studies have disclosed the ability of human plasma and serum to remove penicillin determinants covalently attached to human se- albumin by amide and disulfide bonds. These activities will characterized and their relationship to clinical reactions to penicillin will be assessed. These interrelated studies will provide new general approaches and significant new insights into the immunochemistry, diagnosis, and desensitization of beta-lactam drug allergy.