{"id":22925,"date":"2025-11-24T10:27:09","date_gmt":"2025-11-24T15:27:09","guid":{"rendered":"https:\/\/www.ices.on.ca\/?post_type=journal_article&#038;p=22925"},"modified":"2025-11-28T10:31:32","modified_gmt":"2025-11-28T15:31:32","slug":"trimethoprim-sulfamethoxazole-and-acute-respiratory-failure-in-adolescents-and-young-adults","status":"publish","type":"journal_article","link":"https:\/\/www.ices.on.ca\/fr\/publications\/journal-articles\/trimethoprim-sulfamethoxazole-and-acute-respiratory-failure-in-adolescents-and-young-adults\/","title":{"rendered":"Trimethoprim-sulfamethoxazole and acute respiratory failure in adolescents and young adults"},"content":{"rendered":"<p><strong>Importance<\/strong> \u2014 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.<\/p>\n<p><strong>Objective<\/strong> \u2014 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.<\/p>\n<p><strong>Design, setting, and participants<\/strong> \u2014 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.<\/p>\n<p><strong>Exposure<\/strong> \u2014 TMP-SMX for 3 days or more.<\/p>\n<p><strong>Main outcomes and measures<\/strong> \u2014 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.<\/p>\n<p><strong>Results<\/strong> \u2014 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.<\/p>\n<p><strong>Conclusions and relevance<\/strong> \u2014 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.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Importance \u2014 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. Objective \u2014 To examine the 30-day risk of a hospital visit (ie, hospitalization or emergency department visit) with acute respiratory failure [&hellip;]<\/p>\n","protected":false},"template":"","migration-helper-automated":[],"migration-manual":[],"topic":[16,56],"migration-helper-qa-sample-set":[],"class_list":["post-22925","journal_article","type-journal_article","status-publish","hentry","topic-children-and-young-people","topic-pharmacoepidemiology-and-drug-safety"],"acf":{"citation":"Ahmadi F, McArthur E, Garcia-Bournissen F, Rieder MJ, Muanda FT. <em>JAMA Netw Open<\/em>. 2025; 8(11): e2545251.","source_url":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2025.45251","ices_scientist":[13130],"site":[6739],"research_program":[6743],"news_release":"","journal_article":"","atlas":"","research_report":"","infographic":"","video":"","downloads":null,"links":null,"sitecore_item_id":"","sitecore_item_name":"","sitecore_field_values":"","previous_url":""},"yoast_head":"<!-- This site is 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