Allergy to penicillin unsuccessfully treated with a haptenic inhibitor (benzyl‐penicilloyl‐N₂‐formil‐lysine; BPO‐Flys)

Abstract

In a patient with a past history of allergy to penicillin and requiring treatment, skin tests with penicillin and penicilloyl-polylysine (PPL) were positive, and a penicilloyl RAST was strongly positive, although the Prausnitz-Kustner test to penicillin and PPL were negative. The hapten BPO-Flys was administered together with penicillin to try to prevent reactions. An anaphylactic reaction occurred on the fifth day, and treatment was stopped. Serum total IgE values increased markedly after the reaction and PK titres to penicillin and PPL reached values of 1/256. The skin test reaction to PPL was negative the day after the clinical reaction, but became strongly positive again a few days later. The penicilloyl RAST remained strongly positive throughout. The authors consider that there was hypersensitivity to a penicillin metabolite other than the penicilloyl group, e.g. to minor determinants, and for this reason the hapten inhibitor failed.

Immediate hypersensitivity reactions to penicillin and related antibiotics

“…Univalent hapten inhibitors such as BPO-N:-formyllysine initially showed promise for the treatment of hypersensitivity reactions to penicillin [64 66], but subsequent clinical studies revealed that up to 38% of subjects skin tested had positive skin reactions with the putative hapten itself. Furthermore, the hapten did not always prevent anaphylactic reactions [67].…”

Identification of new minor metabolites of penicillin G in human serum by multiple‐stage tandem mass spectrometry

“…Hypersensitivity reactions to penicillins are due to different metabolite formed in vivo when the antibiotic is administered. [13] After the administration of PCN G, the b-lactam ring irreversibly opens during nucleophilic attack, resulting in the formation of penicilloyl metabolites and the covalent binding to tissue macromolecules to produce the hapten-protein complex and induce immune response. According to previous studies, penicillin metabolites are divided into two groups: major determinants and minor determinants.…”