SELECTED ARTICLES FROM THE RECENT LITERATURE 2004

11/30/04

Cross-reactivity between sulfonamide antibiotics and non-antibiotics

Summary
Background - Concerns persist in some quarters about the possible cross-allergenicity between sulfonamide antibiotics (S-ABx) such as trimethoprim-sulfa and those non-ABx drugs which contain the sulfonamide (Sulf) moiety. This often leads to with holding of Sulf-containing drugs such as furosemide, thiazides, some oral anti-diabetic drugs, and celecoxib from individuals with histories of allergies to S-ABx with obvious therapeutic implications.

Findings - Brackett et al of the Ohio State Univ College of Pharmacy reviewed available data in this area. They pointed out that human immune reactions against the Sulf central structure s have not been delineated as a cause of adverse reactions. Immediate type hypersensitivity reactions to S-ABx appear to be directed against either: 1) a N1 substituted heterocyclic ring in a side-chain of the S-ABx or 2) reactive metabolites formed at the N4 amino nitrogen of the S-ABx molecule that, induce humoral immune or cytotoxic responses. Neither of these components are present in Sulf-containing non-ABx. Thus, these types of immune responses against S-ABx are very unlikely to be directed against Sulf-containing non-ABx.

A small percentage of adverse reactions to S-ABx appears to be due to a T lymphocyte-mediated reactions against a yet undetermined Sulf component. Thus, theoretically there could be a cross-reaction between S-ABx and Sulf-containing non-ABx. However, this has never been proved.

Reference
Pharmacotherapy 2004;24:856-70

Editor's Comments
These comments are similar in most responses to that in previous discussions of this subject reviewed by me previously in this AADMC website. Although the T cell mediated responses described above could theoretically be directed against the central Sulf moiety, epidemiologic studies do not suggest a clinically manifest cross-allergenicity between S-ABx and non-ABx (see Drug Saf 2001;24:239-47 and N Eng J Med 2003;349:1628-35 for other reports describing such studies).

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