Studies on the Mechanism of Penicillin-Induced Fever

Abstract

Fever is one of the most common manifestations of allergy to penicillin (i). In unsensitized individuals, the febrile response typically appears on the 7th-10th day of drug administration, but occurs more rapidly in previously sensitized individuals (2). Despite the frequency and clinical importance of this phenomenon, the factors which produce penicillin (PCN)i-induced fever do not appear to have been investigated.In a search for possible allergens in the normal metabolism of benzylpenicillin G in the host, Levine (3-5) has demonstrated that an initial breakdown product, benzylpenicillenic acid, may be metabolized to the benzylpenicilloyl (BPO) hapten which produces cutaneous penicillin hypersensitivity in rabbits. Further, rabbits sensitized to benzylpenicillin develop serum antibodies specific to BPO as demonstrated by precipitin techniques (5, 6), passive cutaneous anaphylaxis (5, 7, 8), and hemagglutination inhibition (9).Certain immediate reactions of hypersensitivity in man, such as anaphylaxis, have been shown to be caused primarily by minor penicillin determinants such as benzylpenicilloate, benzylpenicillamine, and penicilloate (7, 10, 11); reactions such as rashes, arthritis, and fever which appear later (12) are thought to be due to the BPO hapten. The nature of the antibody responsible for the allergic reaction that produces fever has not been identified, although the delay in onset of this reaction in sensitized individuals suggests an antibody of the IgG class.The purpose of the experiments described here was to determine whether the penicilloyl hapten, in the form of a penicillin-rabbit serum protein conjugate, would produce fevers in rabbits sensitized to penicillin and, if so, to determine what immunologic factors might be responsible for the release of the endogenous pyrogen (EP) that presumably mediates this as well as other forms of hypersensitivity fever (13).

Respiratory disease due to sulphasalazine

“…Sulphasalazine at 1 mg/ml in 001 M phosphate buffered saline pH 7-2 (PBS) was centrifuged at 10,000/? for 10 min and the supernatant coupled to the patient's red cells and rabbit red cells (Chusid & Atkins, 1972) and to formolized tanned sheep red cells (Metlors ct al., 1959). Haemagglutinating titres Correspondence: Dr A. Sealon.…”

Vancomycin‐Induced Neutropenia Associated With Fever: Similarities Between Two Immune‐Mediated Drug Reactions

“…28 It results in formation of drug-antibody immune complexes, lymphocyte sensitization, and release of fever-inducing lymphokines. 19,29,30 Classic signs of allergic reactions such as eosinophilia, urticaria, and anaphylaxis are generally not features of this disorder. 31 The appearance of neutropenia and fever in our patient was likely due to vancomycin based on its abrupt resolution after drug discontinuation and a negative fluconazole rechallenge.…”

“…The ␤-lactams have perhaps the best-described allergic reaction data, and both penicillininduced neutropenia and drug fever have been studied extensively and are documented to have been caused by immune-mediated mechanisms. 29,32 In fact, in a number of patients both disorders have occurred simultaneously. 33 Therefore, it may not be surprising that the two would occur simultaneously in our patient due to a similar hypersensitivity reaction.…”

Clinical study of drug fever induced by parenteral administration of antibiotics.

“…In some cases, especially in those of penicillin allergy, production of antibody and subsequent antigenantibody reaction have been suggested as a cause of fever (Levine 1966;Chusid and Atkins 1972). Hypersensitivity of type IV may also participate in the development of drug fever (Dinarello 1981).…”