{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T10:25:27Z","timestamp":1787307927352,"version":"build-2736575974"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"1211","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The choice of the fourth drug in anti-tubercular therapy for adults with tuberculous meningitis (TBM) remains uncertain. This trial compared the effectiveness and safety of ethambutol (ETM) versus streptomycin (STM) during the intensive phase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is an investigator-initiated, single-center, open-label, randomized controlled trial conducted during October 2020\u2013June 2025. The study was stopped early because of slow recruitment. Patients were randomized to receive either STM (15\u00a0mg\/kg intramuscular daily; ~90 injections) with isoniazid (H) 5\u00a0mg\/kg (~300\u00a0mg\/d), rifampicin (R) 10\u00a0mg\/kg (~600\u00a0mg\/d), and pyrazinamide (Z) 25\u00a0mg\/kg (~1500\u00a0mg\/d), or ETM (15\u00a0mg\/kg orally daily) with HRZ for 6\u00a0months, followed by RH for 12\u00a0months in both arms. Primary outcome was mortality at 6\u00a0months. Secondary outcomes included in-hospital mortality and neurologic disability at 3 and 6\u00a0months. The disability was assessed using the modified Rankin Scale (mRS) as good (mRS\u00a0\u2264\u00a02) or poor (mRS\u2009&amp;gt;\u20092). Adverse events were noted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 131 patients screened, 49 were excluded. The results therefore are based on 82 patients. The two arms were matched for baseline characteristics. At 6\u00a0months, 26 patients had died: 12\/42 (28.6%) in the STM arm and 14\/40 (35%) in the ETM arm (hazard ratio: 0.78; 95% confidence interval: 0.36\u20131.70; P\u00a0=\u20090.54). In intention-to-treat analysis, there were no differences in in-hospital mortality and disability at 3 and 6\u00a0months. Two patients each developed ototoxicity and vision loss in the STM and the ETM arm, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In adults with TBM, there was no difference in mortality or disability at 6\u00a0months between ETM and STM arms, but the study may lack statistical power to detect a difference.<\/jats:p>\n                    <jats:p>The trial was registered in the Clinical Trials Registry of India, CTRI\/2020\/07\/026423 (registered on: 7 July 2020).<\/jats:p>\n                    <jats:p>Key messages What is already known on this topic: The choice of the fourth drug in anti-tubercular therapy (ATT) for adults with tuberculous meningitis (TBM) remains uncertain. Despite extensive use, direct comparisons of ethambutol (ETM) versus streptomycin (STM) in TBM through randomized controlled trials are lacking. What this study adds: In adults with TBM, there was no difference in mortality or disability at 6\u00a0months between ETM- or STM-based ATT regimens during the intensive phase. How this study might affect research, practice, or policy: The safety profile of both drugs was comparable; hence, the choice of fourth drug may instead be guided by safety and feasibility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/postmj\/qgag021","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T12:49:04Z","timestamp":1770814144000},"page":"826-832","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of ethambutol versus streptomycin during the intensive phase in treatment of tuberculous meningitis: an open-label randomized clinical trial"],"prefix":"10.1093","volume":"102","author":[{"given":"Mritunjai","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Neurology, All India Institute of Medical Sciences , Veer Bhadra road, Rishikesh, Dehradun, Uttarakhand 249203 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anu","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Neurology, All India Institute of Medical Sciences , Veer Bhadra road, Rishikesh, Dehradun, Uttarakhand 249203 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajni","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, All India Institute of Medical Sciences , Veer Bhadra road, Rishikesh, Dehradun, Uttarakhand 249203 ,","place":["India"]},{"name":"Tehri Hydro Development Corporation Limited , Pragatipuram, By Pass Road, Rishikesh, Dehradun, Uttarakhand 249201 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Dhar","sequence":"additional","affiliation":[{"name":"Department of Neurology, All India Institute of Medical Sciences , Veer Bhadra road, Rishikesh, Dehradun, Uttarakhand 249203 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagbir","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Neurology, All India Institute of Medical Sciences , Veer Bhadra road, Rishikesh, Dehradun, Uttarakhand 249203 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Neurology, All India Institute of Medical Sciences , Kunraghat, Gorakhpur, Uttarpradesh 273008 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5863-2532","authenticated-orcid":false,"given":"Niraj","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neurology, All India Institute of Medical Sciences , Bibinagar, Hyderabad Metropolitan Region, Telangana 508126 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"2026082105414230700_ref1","doi-asserted-by":"publisher","first-page":"e0000069","DOI":"10.1371\/journal.pgph.0000069","article-title":"The global burden of tuberculous meningitis in adults: a modelling study","volume":"1","author":"Dodd","year":"2021","journal-title":"PLOS Glob Public Health"},{"key":"2026082105414230700_ref2","doi-asserted-by":"publisher","first-page":"ofaf503","DOI":"10.1093\/ofid\/ofaf503","article-title":"Intensified treatment of tuberculous meningitis in adults: a systematic review and meta-analysis. 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