{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:17:06Z","timestamp":1790745426076,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIH\/National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01 AI091429"],"award-info":[{"award-number":["U01 AI091429"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH\/National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["L30 AI120170"],"award-info":[{"award-number":["L30 AI120170"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH\/National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1 AI068636"],"award-info":[{"award-number":["UM1 AI068636"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ronda Stryker and William Johnston Fellowship in Global Health and Social Medicine"},{"name":"Dr. Lynne Reid\/Drs. Eleanor and Miles Shore Fellowship at Harvard Medical School"},{"name":"Burke Global Health Fellowship at the Harvard Global Health Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>We examined whether increased rifampin doses could shorten standard therapy for tuberculosis without increased toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the differences across three daily oral doses of rifampin in change in elimination rate of Mycobacterium tuberculosis in sputum and frequency of rifampin-related adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a blinded, randomized, controlled phase 2 clinical trial of 180 adults with new smear-positive pulmonary tuberculosis, susceptible to isoniazid and rifampin. We randomized 1:1:1 to rifampin at 10, 15, and 20 mg\/kg\/d during the intensive phase. We report the primary efficacy and safety endpoints: change in elimination rate of M. tuberculosis log10 colony-forming units and frequency of grade 2 or higher rifampin-related adverse events. We report efficacy by treatment arm and by primary (area under the plasma concentration\u2013time curve [AUC]\/minimum inhibitory concentration [MIC]) and secondary (AUC) pharmacokinetic exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Each 5-mg\/kg\/d increase in rifampin dose resulted in differences of \u22120.011 (95% confidence interval, \u22120.025 to +0.002; P\u2009=\u20090.230) and \u22120.022 (95% confidence interval, \u22120.046 to \u22120.002; P\u2009=\u20090.022) log10 cfu\/ml\/d in the modified intention-to-treat and per-protocol analyses, respectively. The elimination rate in the per-protocol population increased significantly with rifampin AUC0\u20136 (P\u2009=\u20090.011) but not with AUC0\u20136\/MIC99.9 (P\u2009=\u20090.053). Grade 2 or higher rifampin-related adverse events occurred with similar frequency across the three treatment arms: 26, 31, and 23 participants (43.3%, 51.7%, and 38.3%, respectively) had at least one event (P\u2009=\u20090.7092) up to 4 weeks after the intensive phase. Treatment failed or disease recurred in 11 participants (6.1%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings of more rapid sputum sterilization and similar toxicity with higher rifampin doses support investigation of increased rifampin doses to shorten tuberculosis treatment.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT 01408914).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201712-2524oc","type":"journal-article","created":{"date-parts":[[2018,6,29]],"date-time":"2018-06-29T03:02:42Z","timestamp":1530241362000},"page":"657-666","source":"Crossref","is-referenced-by-count":102,"title":["Efficacy and Safety of High-Dose Rifampin in Pulmonary Tuberculosis. 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