{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:31:02Z","timestamp":1792467062078,"version":"4.5.0"},"reference-count":87,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Sulfamethoxazole\u2013trimethoprim (SMX\u2010TMP) is a widely used antibiotic for treating bacterial infections, but its safety in adult outpatients remains understudied. This systematic review and meta\u2010analysis evaluated the safety profile of SMX\u2010TMP and identified critical research gaps. The pharmacovigilance study aimed to validate and extend findings from meta\u2010analyses to better understand the real\u2010world safety of SMX\u2010TMP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We searched MEDLINE and Embase up to 12 August 2024, to identify studies comparing adverse drug events (ADEs) following SMX\u2010TMP\n                      <jats:italic>vs<\/jats:italic>\n                      . other antibiotics in adult outpatients. Meta\u2010analyses were performed where data allowed. A pharmacovigilance study using the Food and Drug Administration Adverse Event Reporting System was conducted to supplement our findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our review, which included 43 studies, found SMX\u2010TMP had a nearly 3\u2010fold higher risk of rash compared to other antibiotics (pooled risk ratio 2.56, 95% confidence interval [1.69, 3.89],\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u20090%,\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u00a04458 participants, 24 randomized control trials). Pharmacovigilance data confirmed a higher frequencies of skin disorders and other ADEs compared to various comparator drugs. Compared to azithromycin, SMX\u2010TMP was associated with a 5\u2010fold increase in Stevens\u2013Johnson syndrome, a 3\u2010fold increase in toxic epidermal necrolysis, and a 10\u2010fold increase in drug reaction with eosinophilia and systemic symptoms. Additionally, SMX\u2010TMP showed a 10\u2010fold increase in reports of pancytopenia, a 6\u2010fold increase in neutropenia, a 4\u2010fold increase in both thrombocytopenia and aplastic anaemia, a 56\u2010fold increase in hyperkalaemia, and a 10\u2010fold increase in hyponatraemia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our meta\u2010analyses and pharmacovigilance study suggested SMX\u2010TMP was associated with increased risk of ADEs compared to other antibiotics including amoxicillin\/clavulanate, azithromycin and nitrofurantoin. Further robust research is essential to confirm these safety signals and guide clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70051","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T19:59:46Z","timestamp":1743019186000},"page":"1632-1648","source":"Crossref","is-referenced-by-count":22,"title":["Safety of sulfamethoxazole\u2013trimethoprim for the treatment of bacterial infection in outpatient settings: A systematic review and meta\u2010analysis with active comparator disproportionality analysis"],"prefix":"10.1002","volume":"91","author":[{"given":"Rebecca","family":"Preyra","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujain Ez","family":"Eddin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  London Ontario Canada"},{"name":"ICES Western  London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"ICES Western  London ON Canada"},{"name":"Department of Epidemiology &amp; Biostatistics Western University  London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atefeh","family":"Jafari","sequence":"additional","affiliation":[{"name":"ICES Western  London ON Canada"},{"name":"Department of Epidemiology &amp; Biostatistics Western University  London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4682-6564","authenticated-orcid":false,"given":"Flory T.","family":"Muanda","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  London Ontario Canada"},{"name":"ICES Western  London ON Canada"},{"name":"Department of Epidemiology &amp; Biostatistics Western University  London ON Canada"},{"name":"Lawson Health Research Institute, London Health Sciences Centre  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03261973"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.16201"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.4065\/74.7.730"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.111152"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0302\u20102838(02)00270\u20131"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.163.4.402"},{"key":"e_1_2_10_8_1","volume-title":"StatPearls","author":"Kemnic TR","year":"2024"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/4.2.429"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12735"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01715834"},{"key":"e_1_2_10_12_1","unstructured":"Teva Canada Limited.Product monograph \u2010 Teva\u2010trimel DS tablets. 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