TMP-SMX Linked to Higher Risk of Acute Respiratory Failure in Young adults: JAMA
A new study published in the Journal of American Medical Association showed that adolescents and young adults (ages 10–25) taking trimethoprim-sulfamethoxazole (TMP-SMX) had a nearly 3-fold increased incidence of hospital visits for severe respiratory failure when compared to those treated with amoxicillin or cephalosporins.
The US Food and Drug Administration (FDA) has changed the label and issued a warning about a possible link between trimethoprim-sulfamethoxazole (TMP-SMX) and abrupt respiratory failure in young adults and adolescents in good health. Thus, this study compared new users of amoxicillin or a cephalosporin with newly dispensed oral TMP-SMX in order to determine the 30-day risk of a hospital visit (i.e., hospitalization or emergency department visit) with acute respiratory failure in adolescents and young adults aged 10 to younger than 25 years.
Linked administrative health care data was employed in this research conducted in Ontario, Canada between 2003 and 2023. Adolescents and young adults between the ages of 10 and under 25 who had recently received oral TMP-SMX, amoxicillin, or cephalosporins for three or more days from an outpatient pharmacy were included in the TMP-SMX vs. amoxicillin and TMP-SMX vs. cephalosporins groups.
The main outcome was a composite outcome of the 30-day risk of an acute respiratory failure hospital visit (defined as receiving mechanical ventilation, tracheotomy, or extracorporeal membrane oxygenation or being diagnosed with acute respiratory failure). The individual parts of the composite result, all-cause hospitalization, and all-cause death were secondary outcomes.
TMP-SMX users were mostly female and younger (median age of 19) in both matched cohorts. TMP-SMX had a somewhat increased risk of the composite outcome than amoxicillin or cephalosporins, despite the incredibly low absolute event rates. Weighted studies showed small absolute risk differences of around 0.02% and a nearly twofold higher relative risk. These conclusions were validated by sensitivity analysis.
Overall, these results imply that individuals taking TMP-SMX had a greater 30-day probability of hospitalization due to acute respiratory failure than those receiving amoxicillin or cephalosporins. These results corroborated the FDA's warning, and if they are repeated, the advantages and disadvantages of using TMP-SMX should be carefully considered. The FDA warning could be reaffirmed by regulatory bodies, and product monographs and prescription recommendations should be updated and modified appropriately.
Source:
Ahmadi, F., McArthur, E., Garcia-Bournissen, F., Rieder, M. J., & Muanda, F. T. (2025). Trimethoprim-sulfamethoxazole and acute respiratory failure in adolescents and young adults. JAMA Network Open, 8(11), e2545251. https://doi.org/10.1001/jamanetworkopen.2025.45251
