{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:02:31Z","timestamp":1780095751208,"version":"3.54.0"},"posted":{"date-parts":[[2026,3,16]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["R01AI146095"],"award-info":[{"award-number":["R01AI146095"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,29]]},"abstract":"<jats:p>Background: Peripheral neuropathy frequently leads to linezolid dose reductions or interruptions during multidrug- or rifampicin-resistant tuberculosis (MDR\/RR-TB) treatment. The implications of these modifications on treatment success are uncertain. Methods: We conducted a target trial emulation using the endTB Observational Study among individuals who developed non-severe peripheral neuropathy while receiving linezolid 600 mg daily within 6 months of initiating an individualized MDR\/RR-TB regimen. We examined three linezolid management strategies: immediate change (i.e., dose reduction, temporary interruption, discontinuation) within Weeks 1-7 after peripheral neuropathy onset, deferred change within Weeks 8-26, and no change (i.e., continuing linezolid 600 mg daily) during Weeks 1-26. To emulate the per-protocol analysis of a trial, we used an approach involving cloning and censoring participant data, and applying inverse probability of censoring weights. Results: Among 303 eligible participants from 12 countries, peripheral neuropathy occurred a median of 11 weeks (interquartile range: 4-18) after treatment initiation. Weighted, standardized probabilities of treatment success were 84.7% (95% CI: 69.2%, 92.9%) for immediate change, 78.9% (95% CI: 65.9%, 87.1%) for deferred change, and 85.2% (95% CI: 80.5%, 89.1%) for no change. Compared with no change, treatment success ratios were 0.99 (95% CI: 0.83, 1.11) for immediate change and 0.93 (95% CI: 0.78, 1.01) for deferred change. Conclusions: We did not find evidence of a substantial negative impact of immediate modification to linezolid on MDR\/RR-TB treatment success. Our results support the clinical practice of cautiously adjusting linezolid when needed to manage non-severe peripheral neuropathy.<\/jats:p>","DOI":"10.64898\/2026.03.14.26348377","type":"posted-content","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:19Z","timestamp":1773705619000},"source":"Crossref","is-referenced-by-count":0,"title":["Comparison of three linezolid management strategies for peripheral neuropathy in multidrug- or rifampicin-resistant tuberculosis treatment: a target trial emulation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3038-0644","authenticated-orcid":false,"given":"Matthew L","family":"Romo","sequence":"first","affiliation":[{"name":"Harvard Medical School;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"LaHood","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole D","family":"Mitnick","sequence":"additional","affiliation":[{"name":"Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA; Partners In Health, Boston, Massachusetts, USA; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L","family":"Rich","sequence":"additional","affiliation":[{"name":"Partners In Health, Boston, Massachusetts, USA; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Trevisi","sequence":"additional","affiliation":[{"name":"Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Skrahina","sequence":"additional","affiliation":[{"name":"National TB Control Program, Minsk, Belarus;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Oyewusi","sequence":"additional","affiliation":[{"name":"Ministry of Health, Maseru, Lesotho;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Bastard","sequence":"additional","affiliation":[{"name":"Epicentre, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palwasha Y","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; Interactive Research & Development, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Huerga","sequence":"additional","affiliation":[{"name":"Epicentre, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uzma","family":"Khan","sequence":"additional","affiliation":[{"name":"Interactive Research & Development Global, Singapore; McGill University, Department of Epidemiology, Biostatistics and Occupational Health, Montreal, QC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Herrera Flores","sequence":"additional","affiliation":[{"name":"National Hospital Arzobispo Loayza, Lima District, Peru;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakob","family":"Atshemyan","sequence":"additional","affiliation":[{"name":"National Center for Infectious Diseases, Abovyan, Armenia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Hewison","sequence":"additional","affiliation":[{"name":"Medecins Sans Frontieres, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmud","family":"Rashitov","sequence":"additional","affiliation":[{"name":"Partners In Health, Almaty, Kazakhstan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazgul","family":"Samieva","sequence":"additional","affiliation":[{"name":"Medecins Sans Frontieres, Bishkek, Kyrgyzstan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Gomez-Restrepo","sequence":"additional","affiliation":[{"name":"Medecins Sans Frontieres, Yangon, Myanmar;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6417-2738","authenticated-orcid":false,"given":"Aga","family":"Krisnanda","sequence":"additional","affiliation":[{"name":"Interactive Research & Development, Jakarta, Indonesia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinatin","family":"Kotrikadze","sequence":"additional","affiliation":[{"name":"Medecins Sans Frontieres, Tbilisi, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Siraj","sequence":"additional","affiliation":[{"name":"National TB Control Program, Ministry of National Health Services, Regulations & Coordination, Ministry of Health of Pakistan, Karachi, Pakistan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Wali","family":"Khan","sequence":"additional","affiliation":[{"name":"National TB Control Program, Ministry of National Health Services, Regulations & Coordination, Ministry of Health of Pakistan, Karachi, Pakistan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Ndjeka","sequence":"additional","affiliation":[{"name":"National Department of Health, Pretoria, South Africa;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik","family":"Adenov","sequence":"additional","affiliation":[{"name":"National TB Program, Kazakhstan Ministry of Health, Almaty, Kazakhstan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwonjune","family":"Seung","sequence":"additional","affiliation":[{"name":"Partners In Health, Boston, Massachusetts, USA; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andargachew","family":"Kumsa","sequence":"additional","affiliation":[{"name":"Partners In Health, Addis Ababa, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly F","family":"Franke","sequence":"additional","affiliation":[{"name":"Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.14.26348377","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T22:20:12Z","timestamp":1780093212000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.03.14.26348377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,16]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.03.14.26348377","relation":{},"subject":[],"published":{"date-parts":[[2026,3,16]]},"subtype":"preprint"}}