Penicillins and cephalosporins as allergens — structural aspects of recognition and cross‐reactions

Molecular Immunology Unit, Kolling Institute of Medical Research, Royal North Shore Hospital of Sydney and Departmentof Medicine, University of Sydney, Sydney, New South Wales, AustraliaAlthough a wide range of chemically different antibacterialsare used clinically, the b-lactam drugs, principally thepenicillins and cephalosporins, are the most commonlyprescribed antibiotics and the most common drug allergiesseen clinically.Penicillins‘Major’ and ‘minor’ determinantsFrom the perspective of drug allergy, penicillins are the bestknown and most intensively studied b-lactam antibiotics. Allpenicillins contain both a b-lactam and a thiazolidine ring andindividual penicillins are distinguished by the nature of theside-chain group R (Fig. 1). Extensive investigations over aperiod of more than 30years [1–4] identied a number ofultimately proven, and some putative, antigenic determinantsand, on the basis of ring modications and the point ofattachment of protein carrier, determinants have been desig-nated ‘major’ or ‘minor’ [5] (Fig. 1). These are quantitativeterms referring to the amounts of drug conjugates formed.Approximately 95% of penicillin molecules that becomecovalently bound to protein under physiological conditionsform penicilloyl groups and it is this quantitative predomi-nance rather than clinical or immunological importance thatthe term ‘major’ refers to. A variety of other conjugatesincluding penicillenate, penicilloic acid, penicillanyl, pena-maldate, penaldate,