Trimethoprim-sulfamethoxazole-associated respiratory failure: a rapid review of the literature.

Abstract

Introduction: Trimethoprim-sulfamethoxazole (TMP-SMX) is a widely used and generally well tolerated antibiotic. Its association with life-threatening respiratory failure was described in a 2019 case series showing high rates of morbidity and mortality. Due to this reporting, public awareness increased, leading to a safety label change by the FDA in 2021 and the publication of cases and studies evaluating this rare adverse reaction.

Areas covered: In this rapid review, we performed a database search in PubMed and Embase to evaluate the progression of TMP-SMX‑associated respiratory failure research from 1 January 2019 to 27 January 2026. The original case series spurred the publication of other case series that collectively improved understanding of pathology and supportive care, and retrospective studies have recently been published. The wide-reaching impact of case reporting on adverse drug reactions has also been observed historically, such as for chloramphenicol and thalidomide.

Expert opinion: Based on expert opinion, continued efforts to evaluate mechanism, clinical course, and risk would be valuable to better understand this underreported and underrecognized reaction. Altogether, the progression of TMP-SMX-associated respiratory failure research since 2019 demonstrates the importance of publishing cases of rare drug reactions and dissemination to the medical community.