A PENICILLOYLATED PROTEIN IMPURITY AS A SOURCE OF ALLERGY TO BENZYLPENICILLIN AND 6-AMINOPENICILLANIC ACID

Abstract

Fractionation of the sodium salt of 6-aminopenicillanic acid (6-A.P.A.) led to the isolation of a high-molecular-weight material which gave strong passive cutaneous anaphylactic reactions in guineapigs. The " purified " 6-A.P.A. no longer elicited a response. It seems likely that this impurity derived from the Escherichia coli preparation used in the production process. A similar proteinaceous impurity was found in commercially available benzylpenicillin. A method for purifying benzylpenicillin was developed. On storage however, a high-molecular-weight substance developed and this may be derived from the penicillin molecule by polymerisation. Thus, not all the immunological activity of the penicillins is due to the penicilloylated protein. It is thought that the administration of purified benzylpenicillin will reduce the level of induction of hypersensitivity and may decrease the number of allergic manifestations if given inadvertently to a penicillin-sensitive patient. Purified benzylpenicillin should not, however, be deliberately given to a patient known to be sensitive. The implications for oral therapy are not yet known.