Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan

Philipp du Cros; Atadjan Khamraev; Zinaida Tigay; Tleubergen Abdrasuliev; Jane Greig; Graham Cooke; Krzysztof Herboczek; Tanya Pylypenko; Catherine Berry; Amrita Ronnachit; David Lister; Sebastian Dietrich; Cono Ariti; Khasan Safaev; Bern-Thomas Nyang'wa; Nargiza Parpieva; Mirzagalib Tillashaikhov; Jay Achar

doi:10.1183/23120541.00537-2020

Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan

ERJ Open Res. 2021 Feb 8;7(1):00537-2020. doi: 10.1183/23120541.00537-2020. eCollection 2021 Jan.

Authors

Philipp du Cros^{1

2}, Atadjan Khamraev³, Zinaida Tigay⁴, Tleubergen Abdrasuliev⁵, Jane Greig^{1

2}, Graham Cooke⁶, Krzysztof Herboczek¹, Tanya Pylypenko⁵, Catherine Berry¹, Amrita Ronnachit⁵, David Lister⁵, Sebastian Dietrich⁷, Cono Ariti⁸, Khasan Safaev⁹, Bern-Thomas Nyang'wa¹, Nargiza Parpieva⁹, Mirzagalib Tillashaikhov⁹, Jay Achar^{1

10}

Affiliations

¹ Manson Unit, Médecins Sans Frontières, London, UK.
² Burnet Institute, Melbourne, Australia.
³ Supreme Council of Karakalpakstan, Nukus, Karakalpakstan.
⁴ Ministry of Health, Nukus, Karakalpakstan.
⁵ Médecins Sans Frontières, Nukus, Uzbekistan.
⁶ Imperial College London, London, UK.
⁷ Médecins Sans Frontières, Berlin, Germany.
⁸ Cardiff University School of Medicine, Cardiff, UK.
⁹ Specialized Scientific Practical Medical Center of Phthisiology and Pulmonology, Tashkent, Uzbekistan.
¹⁰ Karolinska Institutet, Stockholm, Sweden.

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.