Penicillin minor determinants: History and relevance for current diagnosis

To review the history of the penicillin minor determinants and evaluate their relevance for current diagnosis.

Skin testing to detect immunoglobulin E (IgE) sensitivity to penicillins in patients with a history of penicillin allergy has been the subject of more than 55 years of published research involving tens of thousands of patients.

Selection of data was based on its relevance to the objective of this article.

It was established early on that testing with the major penicilloyl determinant using the polyvalent penicilloyl-polylysine (PPL) is negative in a substantial portion (10% to 64%, including recent increases) of those at risk for immediate hypersensitivity reactions. A variety of minor penicillin determinants are clinically significant in that their use in skin testing is essential to detect all those at risk. In particular, a minor determinant mixture of benzylpenicillin, benzylpenicilloate, and benzylpenilloate, used in conjunction with PPL, has been shown in numerous studies to achieve an average negative predictive value (NPV) of 97.9% in history-positive patients. Benzylpenicillin alone, as the sole minor determinant, leaves many skin test-positive patients undiscovered. Use of amoxicillin as an additional minor determinant reagent appears to identify another 2% to 8% of skin test-positive patients in some populations.

IgE skin testing, using both the major and appropriate minor determinants of penicillin, can identify, with a high degree of reliability (NPV ∼97%), penicillin allergy history-positive patients who can receive beta-lactam antibiotics without concern for serious acute allergy, including anaphylaxis. The few false-negative skin tests reported globally are largely confined to minor, self-limited cutaneous reactions.