{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:00:08Z","timestamp":1791316808964,"version":"4.3.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004417","name":"Global Fund to Fight AIDS, Tuberculosis, and Malaria","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004417","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI46095"],"award-info":[{"award-number":["R01AI46095"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In 2019, the World Health Organization called for operational research on all-oral shortened regimens for multidrug- and rifampicin-resistant tuberculosis (MDR\/RR-TB). We report safety and effectiveness of three 9-month all-oral regimens containing bedaquiline (Bdq), linezolid (Lzd), and levofloxacin (Lfx) and reinforced with cycloserine (Cs) and clofazimine (Cfz), delamanid (Dlm) and pyrazinamide (Z), or Dlm and Cfz.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a prospective cohort study of patients initiating treatment for pulmonary MDR\/RR-TB under operational research conditions at public health facilities in Kazakhstan. Participants were screened monthly for adverse events. Participants with baseline resistance were excluded from the study and treated with a longer regimen. We analyzed clinically relevant adverse events of special interest in all participants and sputum culture conversion and end-of-treatment outcomes among individuals who were not excluded.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 510 participants, 41% were women, the median age was 37 years (25th\u201375th percentile: 28\u201349), 18% had a body mass index &amp;lt;18.5\u2005kg\/m2, and 51% had cavitary disease. A total of 399 (78%) initiated Bdq-Lzd-Lfx-Cs-Cfz, 83 (16%) started Bdq-Lzd-Lfx-Dlm-Z, and 28 (5%) initiated Bdq-Lzd-Lfx-Dlm-Cfz. Fifty-eight individuals (11%) were excluded from the study, most commonly due to identification of baseline drug resistance (n = 52; 90%). Among the remaining 452 participants, treatment success frequencies were 92% (95% CI: 89\u201395%), 89% (95% CI: 80\u201394%), and 100% (95% CI: 86\u2013100%) for regimens with Cs\/Cfz, Dlm\/Z, and Dlm\/Cfz, respectively. Clinically relevant adverse events of special interest were uncommon.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>All regimens demonstrated excellent safety and effectiveness, expanding the potential treatment options for patients, providers, and programs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciae305","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T01:21:47Z","timestamp":1717550507000},"page":"1046-1053","source":"Crossref","is-referenced-by-count":13,"title":["Safety and Effectiveness of 3 Novel All-Oral Shortened Regimens for Rifampicin- or Multidrug-Resistant Tuberculosis in Kazakhstan"],"prefix":"10.1093","volume":"79","author":[{"given":"Makhmujan","family":"Rashitov","sequence":"first","affiliation":[{"name":"Partners In Health Kazakhstan , Almaty ,","place":["Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4890-5728","authenticated-orcid":false,"given":"Molly F","family":"Franke","sequence":"additional","affiliation":[{"name":"Department of Global Health and Social Medicine, Harvard Medical School , Boston, Massachusetts ,","place":["USA"]},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, Massachusetts ,","place":["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 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulzhanat","family":"Bekbolatova","sequence":"additional","affiliation":[{"name":"Atyrau Regional Center of Phthisiopulmonology , Atreyu ,","place":["Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Shalimova","sequence":"additional","affiliation":[{"name":"Karaganda Regional Center of Phthisiopulmonology , Karaganda ,","place":["Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gafurzhan","family":"Eshmetov","sequence":"additional","affiliation":[{"name":"Turkistan Regional Center of Phthisiopulmonology , Turkistan ,","place":["Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagit","family":"Bektasov","sequence":"additional","affiliation":[{"name":"National Scientific Center of Phthisiopulmonology , Almaty ,","place":["Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"LaHood","sequence":"additional","affiliation":[{"name":"Department of Global Health and Social Medicine, Harvard Medical School , Boston, Massachusetts ,","place":["USA"]},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Arlyapova","sequence":"additional","affiliation":[{"name":"Partners In Health , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elna","family":"Osso","sequence":"additional","affiliation":[{"name":"Department of Global Health and Social Medicine, Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Askar","family":"Yedilbayev","sequence":"additional","affiliation":[{"name":"World Health Organization, Regional Office for Europe , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandr","family":"Korotych","sequence":"additional","affiliation":[{"name":"World Health Organization, Regional Office for Europe , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisoara","family":"Ciobanu","sequence":"additional","affiliation":[{"name":"World Health Organization, Regional Office for Europe , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Skrahina","sequence":"additional","affiliation":[{"name":"The Republican Scientific and Practical Centre for Pulmonology and Tuberculosis , Minsk ,","place":["Belarus"]}],"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 ,","place":["USA"]},{"name":"Partners In Health , Boston, Massachusetts ,","place":["USA"]},{"name":"Division of Global Health Equity, Brigham and Women's Hospital , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwonjune J","family":"Seung","sequence":"additional","affiliation":[{"name":"Partners In Health , Boston, Massachusetts ,","place":["USA"]},{"name":"Division of Global Health Equity, Brigham and Women's Hospital , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yerkebulan","family":"Algozhin","sequence":"additional","affiliation":[{"name":"Partners In Health Kazakhstan , Almaty ,","place":["Kazakhstan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L","family":"Rich","sequence":"additional","affiliation":[{"name":"Partners In Health , Boston, Massachusetts ,","place":["USA"]},{"name":"Division of Global Health Equity, Brigham and Women's Hospital , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,4]]},"reference":[{"key":"2024101519051442500_ciae305-B1","volume-title":"Global tuberculosis report 2023","author":"World Health Organization","year":"2023"},{"key":"2024101519051442500_ciae305-B2","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1056\/NEJMoa1901814","article-title":"Treatment of highly drug-resistant pulmonary tuberculosis","volume":"382","author":"Conradie","year":"2020","journal-title":"N Engl J Med"},{"key":"2024101519051442500_ciae305-B3","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1016\/S0140-6736(22)02078-5","article-title":"Evaluation of two short standardised regimens for the treatment of rifampicin-resistant tuberculosis (STREAM stage 2): an open-label, multicentre, randomised, non-inferiority trial","volume":"400","author":"Goodall","year":"2022","journal-title":"Lancet"},{"key":"2024101519051442500_ciae305-B4","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1056\/NEJMoa2117166","article-title":"A 24-week, all-oral regimen for rifampin-resistant tuberculosis","volume":"387","author":"Nyang\u2019wa","year":"2022","journal-title":"N Engl J Med"},{"key":"2024101519051442500_ciae305-B5","author":"endTB Clinical Trial Team"},{"key":"2024101519051442500_ciae305-B6","volume-title":"WHO consolidated guidelines on tuberculosis","author":"World Health Organization","year":"2020"},{"key":"2024101519051442500_ciae305-B7","volume-title":"WHO operational handbook on tuberculosis. Module 4: treatment\u2014drug-resistant tuberculosis treatment, 2022 update","author":"World Health Organization","year":"2022"},{"key":"2024101519051442500_ciae305-B8","author":"Joint United Nations Programme on HIV\/AIDS (UNAIDS)"},{"key":"2024101519051442500_ciae305-B9","volume-title":"Global tuberculosis report 2020","author":"World Health Organization","year":"2020"},{"key":"2024101519051442500_ciae305-B10","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1093\/cid\/ciac019","article-title":"Safety of treatment regimens containing bedaquiline and delamanid in the endTB cohort","volume":"75","author":"Hewison","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2024101519051442500_ciae305-B11","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1212\/01.wnl.0000187119.33075.41","article-title":"Evaluation of a clinical screening tool for HIV-associated sensory neuropathies","volume":"65","author":"Cherry","year":"2005","journal-title":"Neurology"},{"key":"2024101519051442500_ciae305-B12","author":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline"},{"key":"2024101519051442500_ciae305-B13","doi-asserted-by":"crossref","first-page":"e0276457","DOI":"10.1371\/journal.pone.0276457","article-title":"Selection bias in multidrug-resistant tuberculosis cohort studies assessing sputum culture conversion","volume":"17","author":"Rodriguez","year":"2022","journal-title":"PLoS One"},{"key":"2024101519051442500_ciae305-B14","doi-asserted-by":"crossref","first-page":"596","DOI":"10.5588\/ijtld.21.0090","article-title":"Sputum culture conversion definitions and analytic practices for multidrug-resistant TB","volume":"25","author":"Rodriguez","year":"2021","journal-title":"Int J Tuberc Lung Dis"},{"key":"2024101519051442500_ciae305-B15","author":"World Health Organization"},{"key":"2024101519051442500_ciae305-B16","author":"Kazakhstan National Tuberculosis Program, Ministry of Health of the Republic of Kazakhstan"},{"key":"2024101519051442500_ciae305-B17","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":"2024101519051442500_ciae305-B18","doi-asserted-by":"crossref","DOI":"10.4081\/monaldi.2021.1679","article-title":"Effectiveness and safety of fully oral modified shorter treatment regimen for multidrug-resistant tuberculosis in Georgia, 2019\u20132020","volume":"91","author":"Avaliani","year":"2021","journal-title":"Monaldi Arch Chest Dis"},{"key":"2024101519051442500_ciae305-B19","doi-asserted-by":"crossref","first-page":"E938","DOI":"10.1093\/cid\/ciac528","article-title":"Bedaquiline, delamanid, linezolid and clofazimine for treatment of pre-extensively drug-resistant tuberculosis","volume":"76","author":"Padmapriyadarsini","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2024101519051442500_ciae305-B20","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1186\/s12879-019-4378-4","article-title":"The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens","volume":"19","author":"Khan","year":"2019","journal-title":"BMC Infect Dis"},{"key":"2024101519051442500_ciae305-B21","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.ijid.2021.03.001","article-title":"Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis","volume":"105","author":"Court","year":"2021","journal-title":"Int J Infect Dis"},{"key":"2024101519051442500_ciae305-B22","doi-asserted-by":"crossref","first-page":"e1126","DOI":"10.1371\/journal.pone.0001126","article-title":"Multidrug-resistant tuberculosis treatment outcomes in Karakalpakstan, Uzbekistan: treatment complexity and XDR-TB among treatment failures","volume":"2","author":"Cox","year":"2007","journal-title":"PLoS One"},{"key":"2024101519051442500_ciae305-B23","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ijtb.2016.01.031","article-title":"Frequency of adverse events observed with second-line drugs among patients treated for multidrug-resistant tuberculosis","volume":"63","author":"Prasad","year":"2016","journal-title":"Indian J Tuberc"},{"key":"2024101519051442500_ciae305-B24","doi-asserted-by":"crossref","first-page":"e58817","DOI":"10.1371\/journal.pone.0058817","article-title":"Serious treatment related adverse drug reactions amongst anti-retroviral na\u00efve MDR-TB patients","volume":"8","author":"Van der Walt","year":"2013","journal-title":"PLoS One"},{"key":"2024101519051442500_ciae305-B25","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1038\/s41591-018-0224-2","article-title":"A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis","volume":"24","author":"Imperial","year":"2018","journal-title":"Nat Med"},{"key":"2024101519051442500_ciae305-B26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1164\/rccm.202001-0135OC","article-title":"Culture conversion in patients treated with bedaquiline and\/or delamanid","volume":"203","author":"Franke","year":"2021","journal-title":"Am J Respir Crit Care Med"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciae305\/58615180\/ciae305.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciae305\/59764806\/ciae305.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciae305\/59764806\/ciae305.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T19:06:23Z","timestamp":1729019183000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/79\/4\/1046\/7687696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,4]]},"references-count":26,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,6,4]]},"published-print":{"date-parts":[[2024,10,15]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciae305","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,10,15]]},"published":{"date-parts":[[2024,6,4]]}}}