The role of major and minor determinants in penicillin allergy testing: Time to revisit an old friend?

J Allergy Clin Immunol Glob. 2023 Jul 3;2(4):100132. doi: 10.1016/j.jacig.2023.100132. eCollection 2023 Nov.

Abstract

Background: Skin testing is an important step in evaluation of penicillin allergic reactions. It includes testing to the following: amoxicillin, benzyl penicillin, and products generated in vivo after penicillin administration, the major determinant hapten penicilloyl-polylysine (PPL) and the minor determinant mixture (MDM). Although PPL and MDM are available as a commercial kit, their supply and cost remain problematic.

Objective: We aimed to evaluate the performance and utility of PPL and MDM in penicillin allergy testing.

Methods: A retrospective audit over a 5-year period was undertaken for those with penicillin testing in a tertiary immunology unit.

Results: In all, 214 patients were identified. Of those patients, 151 (70.6%) were female and the average age was 58 years. Unspecified penicillin was the most common index drug (n = 127 [59.3%]), followed by amoxicillin (n =3 [24.8%]) and amoxicillin-clavulanic acid (n = 21 [9.7%]). The result of skin testing was positive in 23 patients (10.7%); skin prick testing was positive in 10 patients (4.7%), and intradermal testing (IDT) was positive in 13 patients (6.1%), the majority of whom had identified amoxicillin or amoxicillin-clavulanic acid as the index drug (n = 22 [95.7%]). The result of testing to PPL and/or MDM was positive with IDT only (n=5 [23.8%]). PPL and MDM positivity coexisted with a positive reaction to amoxicillin IDT in 2 patients, 1 of whom passed an amoxicillin challenge. Additionally, 2 positive tests to PPL were present with a negative result for MDM; of these 2 positive results, 1 was positive to amoxicillin IDT. In only 1 case were the results of testing for MDM and PPL both positive, with negative results to all native β-lactams tested; the patient tolerated an amoxicillin challenge. Overall, the negative predictive value for both skin prick testing and IDT was 89.5%.

Conclusion: Benzyl penicillin and amoxicillin alone may be sufficient for in vivo testing in suspected individuals with penicillin allergy.

Keywords: Penicillin skin testing; allergic reaction; drug allergy; penicillin.