Cross-reactivity between penicillins and cephalosporins

The prevalence of cross-reactivity between beta lactams is not known precisely. It is a common misconception that cephalosporin allergy occurs in approximately 10% of patients who are allergic to a penicillin. Immune-mediated penicillin hypersensitivity was historically thought to be due solely to the beta-lactam ring structure that is common to all beta-lactam antibiotics (penicillins, cephalosporins, carbapenems and monobactams). However, clinical data show that most reactions occur in response to antigenic molecules in the R1 side-chain that distinguishes individual penicillins and cephalosporins from one anotherRomano 2016.

Recent evidence suggests that less than 1.5% of patients with a confirmed penicillin allergy have a cephalosporin allergyPicard 2019; this rate is similar to the incidence of new drug allergies or reactions to structurally dissimilar medications in patients with prior drug allergiesKhan 2022.

The American Academy of Allergy, Asthma, and Immunology (AAAAI) and the American College of Allergy, Asthma, and Immunology (ACAAI) practice parameter update suggests around 2% of patients with a confirmed penicillin allergy will experience a reaction to a cephalosporin. It also suggests that less than 5% of patients with an unconfirmed penicillin allergy are truly allergic; when patients with an unconfirmed penicillin allergy are given cephalosporins, the chance of a reaction is very low, with a linked probability of around 0.1% (ie 0.05 × 0.02 = 0.001)Khan 2022.

The permissibility of cephalosporins in patients with penicillin hypersensitivity depends on the type of allergy; see:

• nonsevere (immediate or delayed) hypersensitivity
• severe immediate hypersensitivity – also consider the similarity of the beta-lactam R1 side-chain
• severe delayed hypersensitivity.

For definitions of the types of hypersensitivity, see Definition of commonly used antimicrobial hypersensitivity terms.