Penicillin minor determinants: History and relevance for current diagnosis

Publication date: Available online 21 September 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): N. Franklin Adkinson, Louis M. Mendelson, Charlotte Ressler, John C. Keogh

Abstract

Objective

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

Data Sources

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.

Study Selections

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

Results

It was established early on that testing with the major penicilloyl determinant using the polyvalent penicilloyl-polylysine (PPL) is negative in a substantial portion (10-64%, 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 (MDM) 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 skintest- positive patients undiscovered. Use of amoxicillin as an additional minor determinant reagent appears to identify another 2-8% of skin-testpositive patients in some populations.

Conclusion

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.

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