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    Mar 07, 2021
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    Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan.

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    Authors
    du Cros, Philipp
    Khamraev, Atadjan
    Tigay, Zinaida
    Abdrasuliev, Tleubergen
    Greig, Jane
    Cooke, Graham
    Herboczek, Krzysztof
    Pylypenko, Tanya
    Berry, Catherine
    Ronnachit, Amrita
    Lister, David
    Dietrich, Sebastian
    Ariti, Cono
    Safaev, Khasan
    Nyang'wa, Bern-Thomas
    Parpieva, Nargiza
    Tillashaikhov, Mirzagalib
    Achar, Jay
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    Affiliation
    Manson Unit, Médecins Sans Frontières, London, UK; Burnet Institute, Melbourne, Australia; Supreme Council of Karakalpakstan, Nukus, Karakalpakstan; Ministry of Health, Nukus, Karakalpakstan; Médecins Sans Frontières, Nukus, Uzbekistan; Imperial College London, London, UK; Médecins Sans Frontières, Berlin, Germany; Cardiff University School of Medicine, Cardiff, UK; Specialized Scientific Practical Medical Center of Phthisiology and Pulmonology, Tashkent, Uzbekistan; Karolinska Institutet, Stockholm, Sweden
    Issue Date
    2021-02-08
    
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    Journal
    ERJ open research
    Abstract
    Background In 2016, World Health Organization guidelines conditionally recommended standardised shorter 9–12-month regimens for multidrug-resistant (MDR) tuberculosis (TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan. Methods Consecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between September 1, 2013 and March 31, 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion. Results Of 146 enrolled patients, 128 were included: 67 female (52.3%), median age 30.1 (interquartile range 23.8–44.4) years. At the end of treatment, 71.9% (92 out of 128) of patients achieved treatment success, with 68% (87 out of 128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failures with fluoroquinolone-resistance amplification in 8 patients (8 out of 22, 36.4%); 12 (9.4%) lost to follow-up; and 2 (1.5%) deaths. Recurrence occurred in one patient. Fourteen patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (adjusted OR 6.13, 95% CI 2.01; 18.63) and adherence <95% (adjusted OR 5.33, 95% CI 1.73; 16.36) were associated with unsuccessful outcome in multivariable logistic regression. Conclusions Overall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of drug susceptibility testing-confirmed susceptibility.
    URI
    http://hdl.handle.net/10144/619875
    DOI
    10.1183/23120541.00537-2020
    PubMed ID
    33585652
    Type
    Article
    Language
    en
    ISSN
    2312-0541
    ae974a485f413a2113503eed53cd6c53
    10.1183/23120541.00537-2020
    Scopus Count
    Collections
    TB

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