Beta-lactam structure and cross-reactivity

β-lactam antibiotics include penicillins, cephalosporins, carbapenems, and monobactams. Cross-reactivity is possible through the core β-lactam ring, adjacent thiazolidine (penicillin) or dihydrothiazine (cephalosporin) ring, and also from a side chain, R₁, or R₂ group (left panel). Cephalosporins have both an R₁ and R₂ group, while penicillins only have an R₁. Despite varied mechanisms, true cross-reactivity is largely based on R₁ side chains. Identical side chains in patients with immunoglobulin E (IgE)-mediated allergy pose the highest risk. However, cross-reactivity from side chains that are similar, but not identical, and from R₂ group similarity is possible and reported. The center panel demonstrates the structure and rates of cross-reactivity between penicillins, cephalosporins, carbapenems, and monobactams. The right panel details the most clinically important cross-reactivity considerations. Note that these groupings are used to choose alternative drugs to include in a skin testing-based allergy evaluation or other approach to risk assessment. Drugs not included in these groupings should not be assumed to be safe.