{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:17:43Z","timestamp":1789579063807,"version":"build-2803163510"},"reference-count":39,"publisher":"European Respiratory Society (ERS)","issue":"2","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2025,4,6]]},"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The optimal dosing strategy of linezolid for treating multidrug-resistant and rifampicin-resistant tuberculosis remains unclear. We conducted an individual patient data meta-analysis to determine the optimal linezolid dosing strategy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We searched for randomised controlled trials and prospective cohort studies on short-course all\u2011oral regimens containing linezolid for treating multidrug-resistant and rifampicin-resistant tuberculosis in PubMed, Embase and Scopus up to 31 August 2023. Patients were grouped according to linezolid dosing patterns. Time to treatment success and adverse events of grade 3 and higher were analysed using the Fine\u2013Gray sub-distribution hazard model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 12 eligible studies, eight (four randomised controlled trials, four prospective studies) were included. Overall, 945 patients were grouped as follows: group 1 (600\u2005mg\u00b7day<jats:sup>\u22121<\/jats:sup> linezolid for 8\u2005weeks), group 2 (600\u2005mg\u00b7day<jats:sup>\u22121<\/jats:sup> for 16\u2005weeks, then 300\u2005mg\u00b7day<jats:sup>\u22121<\/jats:sup> for 8\u2005weeks), group 3 (600\u2005mg\u00b7day<jats:sup>\u22121<\/jats:sup> for 39\u2005weeks) and group 4 (1200\u2005mg\u00b7day<jats:sup>\u22121<\/jats:sup> for 25\u2005weeks). Proportions of patients achieving treatment success were 59.1%, 90.4%, 91.3% and 96.0%, respectively. Compared with group 2, group 1 (adjusted sub-distribution hazard ratio (SHR) 0.24, 95% CI 0.08\u20130.71) and group 3 (adjusted SHR 0.36, 95% CI 0.16\u20130.81) had lower success rates. While group 4 showed no significant difference in treatment success <jats:italic>versus<\/jats:italic> group 2 (adjusted SHR 0.57, 95% CI 0.23\u20131.43), it had a higher rate of adverse events of grade 3 and higher (adjusted SHR 2.29, 95% CI 1.37\u20133.83).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>A dosing strategy of 600\u2005mg\u00b7day<jats:sup>\u22121<\/jats:sup> linezolid for 16\u2005weeks then 300\u2005mg\u00b7day<jats:sup>\u22121<\/jats:sup> for 8\u2005weeks could be optimal for treating multidrug-resistant and rifampicin-resistant tuberculosis when considering effectiveness and safety.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1183\/13993003.00315-2025","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T15:15:13Z","timestamp":1752765313000},"page":"2500315","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Optimal dosing and duration of linezolid for the treatment of multidrug-resistant and rifampicin-resistant tuberculosis: an individual patient data meta-analysis"],"prefix":"10.1183","volume":"66","author":[{"given":"Nakwon","family":"Kwak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joong-Yub","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3148-1810","authenticated-orcid":false,"given":"Areum","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Beumont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"Tweed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Crook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keertan","family":"Dheda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Fabiane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muse O.","family":"Fadeyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1151-0049","authenticated-orcid":false,"given":"Salah","family":"Foraida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5518-9600","authenticated-orcid":false,"given":"Tinne","family":"Gils","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Thanh Thuy","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menal A.","family":"Jham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binh Hoa","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Mai Phuong","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bern Thomas","family":"Nyang'wa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzette","family":"Oelofse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seokyung","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Joon","family":"Yim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"2025082203353773000_66.2.2500315.1","unstructured":"World Health Organization . Global Tuberculosis Report 2024. Geneva, World Health Organization, 2024."},{"key":"2025082203353773000_66.2.2500315.2","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.5588\/ijtld.17.0468","article-title":"The devil we know: is the use of injectable agents for the treatment of MDR-TB justified?","volume":"21","author":"Reuter","year":"2017","journal-title":"Int J Tuberc Lung Dis"},{"key":"2025082203353773000_66.2.2500315.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2119430"},{"key":"2025082203353773000_66.2.2500315.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1901814"},{"key":"2025082203353773000_66.2.2500315.5","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S2213-2600(23)00389-2","article-title":"Short oral regimens for pulmonary rifampicin-resistant tuberculosis (TB-PRACTECAL): an open-label, randomised, controlled, phase 2B-3, multi-arm, multicentre, non-inferiority trial","volume":"12","author":"Nyang'wa","year":"2024","journal-title":"Lancet Respir Med"},{"key":"2025082203353773000_66.2.2500315.6","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/S0140-6736(22)01883-9","article-title":"9 months of delamanid, linezolid, levofloxacin, and pyrazinamide versus conventional therapy for treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-END): a multicentre, randomised, open-label phase 2\/3 non-inferiority trial in South Korea","volume":"400","author":"Mok","year":"2022","journal-title":"Lancet"},{"key":"2025082203353773000_66.2.2500315.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31644-1"},{"key":"2025082203353773000_66.2.2500315.8","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.11.0451"},{"key":"2025082203353773000_66.2.2500315.9","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00022912"},{"key":"2025082203353773000_66.2.2500315.10","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.ebiom.2015.09.051","article-title":"Linezolid trough concentrations correlate with mitochondrial toxicity-related adverse events in the treatment of chronic extensively drug-resistant tuberculosis","volume":"2","author":"Song","year":"2015","journal-title":"EBioMedicine"},{"key":"2025082203353773000_66.2.2500315.11","doi-asserted-by":"crossref","first-page":"232","DOI":"10.5588\/ijtld.22.0423","article-title":"Risk factors for peripheral neuropathy in patients on linezolid-containing regimens for drug-resistant TB","volume":"27","author":"Kwon","year":"2023","journal-title":"Int J Tuberc Lung Dis"},{"key":"2025082203353773000_66.2.2500315.12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.3656"},{"key":"2025082203353773000_66.2.2500315.13","unstructured":"World Health Organization . WHO Consolidated Guidelines on Tuberculosis. Module 4: Treatment-Drug-Resistant Tuberculosis Treatment, 2022 Update. Geneva, World Health Organization, 2022."},{"key":"2025082203353773000_66.2.2500315.14","unstructured":"World Health Organization . WHO Consolidated Guidelines on Tuberculosis. Module 4: Treatment-Drug-Resistant Tuberculosis Treatment. Geneva, World Health Organization, 2020."},{"key":"2025082203353773000_66.2.2500315.15","unstructured":"Department of Health and Human Services . Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events: Corrected Version 2.1. Bethesda, MD, National Institutes of Health, 2017."},{"key":"2025082203353773000_66.2.2500315.16","unstructured":"M\u00e9decins Sans Fronti\u00e8res . PV-TB-D12 TB Severity Grading Scale. Available from: https:\/\/endtb.org\/toolkit\/endtb-trials-pharmacovigilance\/"},{"key":"2025082203353773000_66.2.2500315.17","unstructured":"National Institutes of Health . Common Terminology Criteria for Adverse Events (CTCAE). 2010. Available from: https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/ctc.htm#ctc_40 Date last accessed: 21 August 2022."},{"key":"2025082203353773000_66.2.2500315.18","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"2025082203353773000_66.2.2500315.19","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i4919"},{"key":"2025082203353773000_66.2.2500315.20","unstructured":"World Health Organization . Meeting Report of the WHO Expert Consultation on Drug-Resistant Tuberculosis Treatment Outcome Definitions. Geneva, World Health Organization, 2021. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240022195"},{"key":"2025082203353773000_66.2.2500315.21","doi-asserted-by":"publisher","DOI":"10.2307\/2670170"},{"key":"2025082203353773000_66.2.2500315.22","doi-asserted-by":"crossref","unstructured":"Kaufman L , Rousseeuw PJ . Finding Groups in Data: An Introduction to Cluster Analysis. Hoboken, NJ, John Wiley & Sons, 1990.","DOI":"10.1002\/9780470316801"},{"key":"2025082203353773000_66.2.2500315.23","doi-asserted-by":"crossref","first-page":"012015","DOI":"10.1088\/1742-6596\/1361\/1\/012015","article-title":"Improved the performance of the k-means cluster using the sum of squared error (SSE) optimized by using the elbow method","volume":"1361","author":"Nainggolan","year":"2019","journal-title":"J Phys Conf Ser"},{"key":"2025082203353773000_66.2.2500315.24","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2022-071349"},{"key":"2025082203353773000_66.2.2500315.25","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1093\/cid\/ciae388","article-title":"Effectiveness and safety of varying doses of linezolid with bedaquiline and pretomanid in treatment of drug-resistant pulmonary tuberculosis: open-label, randomized clinical trial","volume":"79","author":"Padmapriyadarsini","year":"2024","journal-title":"Clin Infect Dis"},{"key":"2025082203353773000_66.2.2500315.26","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac019"},{"key":"2025082203353773000_66.2.2500315.27","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxr032"},{"key":"2025082203353773000_66.2.2500315.28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-842X.2001.tb00294.x"},{"key":"2025082203353773000_66.2.2500315.29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2117166"},{"key":"2025082203353773000_66.2.2500315.30","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1164\/rccm.202107-1779OC","article-title":"An all-oral 6-month regimen for multidrug-resistant tuberculosis: a multicenter, randomized controlled clinical trial (the NExT study)","volume":"205","author":"Esmail","year":"2022","journal-title":"Am J Respir Crit Care Med"},{"key":"2025082203353773000_66.2.2500315.31","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/QAI.0000000000003150","article-title":"Decentralized, integrated treatment of RR\/MDR-TB and HIV using a bedaquiline-based, short-course regimen is effective and associated with improved HIV disease control","volume":"92","author":"Govender","year":"2023","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2025082203353773000_66.2.2500315.32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/inthealth\/ihad023","article-title":"A four-drug standardized short regimen for highly resistant TB in South-West Nigeria","volume":"16","author":"Fadeyi","year":"2024","journal-title":"Int Health"},{"key":"2025082203353773000_66.2.2500315.33","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ijid.2022.11.007","article-title":"Effectiveness and safety of bedaquiline-based, modified all-oral 9\u201311-month treatment regimen for rifampicin-resistant tuberculosis in Vietnam","volume":"126","author":"Nguyen","year":"2023","journal-title":"Int J Infect Dis"},{"key":"2025082203353773000_66.2.2500315.34","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01467-2019"},{"key":"2025082203353773000_66.2.2500315.35","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks201"},{"key":"2025082203353773000_66.2.2500315.36","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05453-11"},{"key":"2025082203353773000_66.2.2500315.37","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00751-17"},{"key":"2025082203353773000_66.2.2500315.38","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1093\/cid\/ciad653","article-title":"The safety and tolerability of linezolid in novel short-course regimens containing bedaquiline, pretomanid, and linezolid to treat rifampicin-resistant tuberculosis: an individual patient data meta-analysis","volume":"78","author":"Hasan","year":"2024","journal-title":"Clin Infect Dis"},{"key":"2025082203353773000_66.2.2500315.39","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1093\/cid\/ciab699","article-title":"Proposed linezolid dosing strategies to minimize adverse events for treatment of extensively drug-resistant tuberculosis","volume":"74","author":"Imperial","year":"2022","journal-title":"Clin Infect Dis"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.00315-2025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T10:35:50Z","timestamp":1755858950000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.00315-2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":39,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,8,22]]},"published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1183\/13993003.00315-2025"],"URL":"https:\/\/doi.org\/10.1183\/13993003.00315-2025","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,17]]}}}