D2.230 - Cross-Reactivity of Cephalosporins in Patients with IgE-Mediated Allergy to Penicillins: A Systematic Review

Despite both being beta-lactams, there is controversy in the literature about the extent of cross-reactivity between cephalosporins and penicilins. Some have contested that the cross-reactivity rates are actually much lower than historically reported due to differences in the side-chains and better purity of cephalosporin synthesis. Despite that, clinicians may stil be reserved despite growing evidence that use of alternative non-beta-lactam antibiotics in penicilin allergy have been shown with poorer clinical outcomes. This systematic review aims to evaluate the risks of cross-reactivity of cephalosporins in patients exhibiting a Type 1 (IgE mediated) alergic reaction to penicilin, and determine the extent and severity of the risk involved, whilst evaluating the side-chain similarity hypothesis, and the type of cephalosporin, and patient characteristics influencing the risks.

Articles that described the outcome when one or more patients, of any age, with a history of symptoms compatible with an IgE-mediated alergy to any penicilin, that subsequently received a minimum of one dose of any cephalosporin, wil be included in this systematic review. Only studies written in English-language, with full text available, wil be included. Articles where the documentation of the allergic reactions to penicilins were not IgE-mediated, or unclear were excluded. A review of the literature from PubMed, Embase, Cochrane Library and Ovid MEDLINE. The following terms “allergy”, “hypersensitivity”, “cross-reactivity”, “penicilins”, “cephalosporins” and “beta-lactams”, along with its variations were searched and combined. References cited within reviews, or cross-cited in Web of Science that met the inclusion criteria wil be hand-searched and added to the database. Data would be categorized by type of cephalosporin, and type of cephalosporin exposure (skin test, oral or parenteral challenge). Clinical outcome data such as presence, type and severity of reactions from cephalosporin exposure would be used in the analysis.

Seventy-four out of 3,551 identified articles were included, giving an overall cross-reactivity rate of 5.9% with a study population of 5,078. Patients with established IgE-mediated penicillin allergy exhibited a higher cross-reactivity rate (8.4%) than those with unspecified mechanisms (1.4%). Patients diagnosed through penicillin challenge (10.4%) and skin test (14.5%) presented with higher rates than those diagnosed via history (2.8%). The first (5.8%) and second-generation (8.6%) cephalosporins presented higher cross-reactivity rates as compared to the third- (1.8%) and fourth-generations (2.1%). The rates for key cephalosporins are as follows: 0.7% for cefazolin, 3.4% for cefuroxime, 1.9% for ceftriaxone, 0.6% for ceftazidime, 2.1% for cefepime, and 42.9% for ceftaroline. 

A single cross-reactivity rate should not be universally applied to all cephalosporins as it is influenced by multiple factors. Evaluation of these factors can help identify opportunities for safe cephalosporin use in penicillin-allergic patients.