TY - JOUR T1 - Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00537-2020 SP - 00537-2020 AU - Philipp du Cros AU - Khamraev Atadjan AU - Tigay Zinaida AU - Tleubergen Abdrasuliev AU - Jane Greig AU - Graham Cooke AU - Krzysztof Herboczek AU - Tanya Pylypenko AU - Catherine Berry AU - Amrita Ronnachit AU - David Lister AU - Sebastian Dietrich AU - Cono Ariti AU - Hasan Safaev AU - Bern-Thomas Nyang'wa AU - Parpieva Nargiza AU - Tillashaikhov Mirzagalib AU - Jay Achar Y1 - 2020/01/01 UR - http://openres.ersjournals.com/content/early/2020/10/15/23120541.00537-2020.abstract N2 - Background In 2016, WHO guidelines conditionally recommended standardised shorter 9–12 month regimens for multidrug-resistant tuberculosis (MDR-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 1st September 2013 and 31st March 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, 128 patients were included: 67 female (52.3%), median age 30.1 (IQR 23.8–44.4) years. At the end of treatment, 71.9% (92/128) patients achieved treatment success, with 68% (87/128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failure with fluoroquinolone resistance amplification in 8 patients (8/22, 36.4%); 12 (9.4%) loss to follow-up; 2 (1.5%) deaths. Recurrence occurred in one patient. 14 patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (aOR 6.13, 95% CI 2.01;18.63) and adherence<95% (aOR 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 DST-confirmed susceptibility.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. du Cros reports other funded work from TB Alliance for introduction of pretomanid, outside the submitted work.Conflict of interest: Dr. Khamraev has nothing to disclose.Conflict of interest: Dr. Tigay has nothing to disclose.Conflict of interest: Dr. Abdrasuliev has nothing to disclose.Conflict of interest: Dr. Greig has nothing to disclose.Conflict of interest: Dr. Cooke has nothing to disclose.Conflict of interest: Dr. Herboczek has nothing to disclose.Conflict of interest: Dr. Pylypenko has nothing to disclose.Conflict of interest: Dr. Berry has nothing to disclose.Conflict of interest: Dr. Ronnachit has nothing to disclose.Conflict of interest: Dr. Lister has nothing to disclose.Conflict of interest: Dr. Dietrich has nothing to disclose.Conflict of interest: Mr. Ariti has nothing to disclose.Conflict of interest: Dr. Safaev has nothing to disclose.Conflict of interest: Dr. Nyang'wa has nothing to disclose.Conflict of interest: Dr. Parpieva has nothing to disclose.Conflict of interest: Dr. Tillashaykhov has nothing to disclose.Conflict of interest: Dr. Achar has nothing to disclose. ER -