Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan
Authorsdu Cros, Philipp
AffiliationManson Unit, Médecins Sans Frontières, London, United Kingdom; Burnet Institute, Melbourne Australia; Supreme Council of Karakalpakstan, Nukus, Karakalpakstan; Ministry of Health, Nukus, Karakalpakstan; Médecins Sans Frontières, Nukus, Uzbekistan; Imperial College London, London, United Kingdom; Médecins Sans Frontières, Berlin, Germany; Cardiff University School of Medicine, Cardiff, United Kingdom; Specialized Scientific Practical Medical Center of phthisiology and Pulmonology, Tashkent, Uzbekistan; Karolinska Institutet, Stockholm, Sweden
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JournalERJ Open Research
AbstractBackground 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.
PublisherEuropean Respiratory Society (ERS)
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc/4.0/