The complex clinical picture of beta-lactam hypersensitivity: penicillins, cephalosporins, monobactams, carbapenems, and clavams

Abstract

Beta-lactam antibiotics are the drugs most frequently involved in drug hypersensitivity reactions that are mediated by specific immunologic mechanisms. In addition to benzylpenicillin, several chemical structures belonging to 5 major subgroups can induce reactions. The most relevant structure is that of the amoxicillin molecule. Reactions belong to the 4 major mechanisms described by Coombs and Gell, whereby type IV reactions have recently been further subclassified. The most frequent reactions are type I, which are IgE mediated, and type IV, which are nonimmediate and T-cell dependent. IgE-specific antibodies may recognize the benzylpenicilloyl structure or another part of the molecule, such as the side chain, as antigenic determinants. Depending on specific recognition, subjects can be either cross-reactors or selective responders. A variety of entities exist in T-cell reactions, ranging from mild exanthema to life-threatening, severe reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis. Diagnostic tests for IgE-mediated reactions can be done in vivo by testing skin with different penicillin determinants or in vitro by quantitating specific IgE antibodies. For nonimmediate reactions, there are also in vitro and in vivo tests, with variable degrees of sensitivity and specificity. The natural history of IgE-mediated reactions indicates that the count of specific IgE antibodies decreases over time and that results of diagnostic tests can become negative.