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Evaluating immediate reactions to cephalosporins: eye on the calendar

Published online: April 1, 2021

Parent drugs are used as skin-test reagents for evaluating subjects with allergic reactions to cephalosporins. However, few studies have assessed the diagnostic value of cephalosporin skin tests in patients with immediate reactions (i.e., occurring within 1-6 hours after the last administered dose, typically within 1 hour).

Romano et al published in The Journal of Allergy and Clinical Immunology: In Practice a prospective study of 236 consecutive subjects who had suffered 249 immediate reactions (158 anaphylaxis) to cephalosporins in order to evaluate the usefulness of skin tests and challenges in assessing such patients. The most frequent responsible compounds were ceftriaxone (157 reactions), cefazolin (19), cefaclor (19), and ceftazidime (17). Skin tests were performed with penicillin reagents and suspected cephalosporins. Serum specific immunoglobulin E (IgE) assays (ImmunoCAP) were also carried out for penicillins and cefaclor. Individuals with negative results underwent challenges with the suspected cephalosporins, and negative patients who had been assessed more than 6 months after their reactions were re-evaluated.

In the first allergy workup, an allergy to cephalosporins was diagnosed in 164 (69.5%) of the 236 patients on the basis of skin-tests (162 patients) or cefaclor ImmunoCAP (2 patients). The mean time interval between the most recent cephalosporin reaction and allergy examination was significantly longer (P < 0.0001) in the 74 subjects negative to cephalosporin skin tests (mean: 50.8 ± 77 months) than in the 162 subjects positive to them (mean: 12.7 ± 38.4 months). Indeed, the rate of positive patients was lower as this time interval increased, decreasing from 82.5% (118/143) of patients assessed within 6 months to 47.3% (44/93) of those evaluated after more than 6 months.
Of the 72 negative patients, 55 underwent cephalosporin challenges: 3 reacted. Twenty subjects were re-evaluated after cephalosporin negative challenges, with a conversion to cephalosporin skin-test positivity occurring in 5 of the 6 subjects who had had anaphylactic reactions and in none of the remaining 14 subjects with other reactions. Overall, an allergy to cephalosporins was diagnosed in 172 patients (including 5 after retesting).

In conclusion, most immediate reactions to cephalosporins are allergic (i.e., IgE-mediated). Skin testing with parent cephalosporins is a useful tool for evaluating these reactions. The time interval between the most recent cephalosporin reaction and allergy examination may influence the sensitivity of the latter. Consequently, in order to avoid false negative results, it is crucial to assess patients with immediate reactions to cephalosporins within a few months. IgE-mediated cephalosporin hypersensitivity may even disappear eventually. Therefore, it is advisable to retest negative patients who experienced anaphylaxis more than 6 months before the allergy workup, including challenges, in order to exclude a possible re-sensitization after loss of sensitivity. On the other hand, this approach has not proven to be useful in subjects with other reactions, such as urticaria and/or angioedema.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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