Beta-lactam crossreactivity

The problem of penicillin allergy was not solved as had been hoped by the introduction of cephalothin, the first cephalosporin, or ampicillin, the first semisynthetic penicillin in the early 1960s. Allergic reactions to these new antibiotics were observed among patients allergic to penicillin shortly after the drugs came into broad use. Subsequent immunochemical studies in animals and man demonstrated a high degree of immunological crossreactivity among all semisynthetic penicillins, and strong but incomplete crossreactivity between penicillins and early cephalosporins. Saxon studied cross-sensitization to imipenin in patients allergic to penicillin and found substantial rates of positive skin tests using imipenem reagents. In the 1980s, the monobactam antibiotic aztreonam was studied. Trivial immunological crossreactivity in animal and human studies were found. We were later able to safely treat 20 patients allergic to penicillin who had positive penicillin skin tests with therapeutic doses of aztreonam without acute allergic reactions. Thus, among the four classes of beta-lactam antibiotics studied to date, most studies report the concept that crossreactivity is virtually complete among the semisynthetic penicillins, there is highly variable and incomplete crossreactivity between penicillins and cephalosporins and penems all of which have bi-cyclic nuclei, and very weak and rare crossreactivity between the other classes of beta-lactams and aztreonam which lacks a second ring adjacent to the beta-lactam nucleus. Taken together these observations strongly suggest that it is the nuclear structure of beta-lactams which largely determines the crossreactivity.