Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan.
Authors
du Cros, PhilippKhamraev, 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
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, SwedenIssue Date
2021-02-08
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ERJ open researchAbstract
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.PubMed ID
33585652Type
ArticleLanguage
enISSN
2312-0541ae974a485f413a2113503eed53cd6c53
10.1183/23120541.00537-2020
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