{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:09:18Z","timestamp":1786975758422,"version":"build-2736575974"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n The US Food and Drug Administration (FDA) has issued a warning and a label change regarding a potential association between trimethoprim-sulfamethoxazole (TMP-SMX) and acute respiratory failure in healthy adolescents and young adults.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To examine the 30-day risk of a hospital visit (ie, hospitalization or emergency department visit) with acute respiratory failure in adolescents and young adults aged 10 to younger than 25 years old newly dispensed oral TMP-SMX compared with new users of amoxicillin or a cephalosporin.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective, population-based, new-user cohort study in Ontario, Canada (2003-2023) used linked administrative health care data. The TMP-SMX vs amoxicillin and TMP-SMX vs cephalosporins cohorts both included adolescents and young adults aged 10 to younger than 25 years who were newly dispensed oral TMP-SMX, amoxicillin, or cephalosporins for 3 or more days from an outpatient pharmacy. Data were analyzed from January 1 to April 30, 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n TMP-SMX for 3 days or more.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was a composite outcome of the 30-day risk of a hospital visit with acute respiratory failure (defined as a diagnosis of acute respiratory failure or receipt of mechanical ventilation, tracheotomy, or extracorporeal membrane oxygenation). Secondary outcomes were the individual components of the composite outcome, all-cause hospitalization, and all-cause mortality. Overlap weighting on the propensity score was used to balance comparison groups on 84 indicators of baseline health. Weighted risk ratios were obtained using log-binomial regression and weighted risk differences using binomial regression. Sensitivity analyses using a negative control outcome, and case-crossover analysis were also performed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The TMP-SMX vs amoxicillin cohort included 575\u202f218 individuals (44\u202f801 TMP-SMX users and 530\u202f417 amoxicillin users; median age after weighting, 19 years [IQR, 16-22 years]; 74.3% female). The TMP-SMX vs cephalosporins cohort included 248\u202f236 individuals (51\u202f197 TMP-SMX users and 197\u202f039 cephalosporin users; median age after weighting, 19 years [IQR, 16-22 years]; 72.3% were female). The risk of the composite outcome occurred in 15 of 44\u202f801 patients (0.03%) who started TMP-SMX and in 49 of 530\u202f417 (0.01%) who started amoxicillin (number of weighted events, 7 of 21\u202f579 [0.03%] for TMP-SMX and 2 of 21\u202f579 [0.01%] for amoxicillin; weighted risk ratio, 2.79 [95% CI, 1.01-7.71]; weighted risk difference, 0.02% [95% CI, 0.001%-0.04%]). The risk of the composite outcome occurred in 17 of 51\u202f197 patients (0.03%) who started TMP-SMX and in 21 of 197\u202f039 (0.01%) who started cephalosporins (number of weighted events, 8 of 20\u202f538 [0.04%] for TMP-SMX and 3 of 20\u202f538 [0.01%] for cephalosporins; weighted risk ratio, 2.85 [95% CI, 1.11-7.31]; weighted risk difference, 0.02% [95% CI, 0.005%-0.05%]). Results were consistent in sensitivity analyses.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n These findings suggest that the 30-day risk of a hospital visit with acute respiratory failure was higher among those receiving TMP-SMX compared with those receiving amoxicillin or cephalosporins. These findings supported the FDA warning, and if replicated, the risks should be carefully weighed against the benefits of TMP-SMX use. Regulatory agencies could reinforce the FDA warning, and product monographs and prescribing guidelines should be updated and revised accordingly.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.45251","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T16:31:03Z","timestamp":1764001863000},"page":"e2545251","source":"Crossref","is-referenced-by-count":4,"title":["Trimethoprim-Sulfamethoxazole and Acute Respiratory Failure in Adolescents and Young Adults"],"prefix":"10.1001","volume":"8","author":[{"given":"Fatemeh","family":"Ahmadi","sequence":"first","affiliation":[{"name":"ICES, Toronto, Ontario, Canada"},{"name":"Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada"},{"name":"London Health Sciences Centre Research Institute, London Health Sciences Centre, London, Ontario, 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