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Journal Article > Research

Culture conversion in patients treated with bedaquiline and/or delamanid: A prospective multi-country study

Franke MF, Khan PY, Hewison CCH, Khan UT, Huerga H, Seung KJ, Rich ML, Zarli K, Samieva N, Oyewusi L, Nair P, Mudassar M, Melikyan N, Lenggogeni P, Lecca L, Kumsa A, Khan MA, Islam S, Hussein K, Docteur W, Chumburidze N, Berikova E, Atshemyan H, Atwood S, Alam MS, Ahmed SM, Bastard M, Mitnick CD, endTB Study Group
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Abstract
BACKGROUND
Bedaquiline and delamanid offer the possibility of more effective and less toxic multidrug-resistant tuberculosis (MDR-TB) treatment. With this treatment, however, some patients, remain at high risk for an unfavorable treatment outcome. The endTB observational study is the largest multicountry cohort of patients with rifampin-resistant/MDR-TB treated in routine care, according to WHO guidance, with delamanid- and/or bedaquiline-containing regimens. We report frequency of sputum culture conversion within six-months of treatment initiation and risk factors for non-conversion.

METHODS
We included patients with a positive baseline culture who initiated a first endTB regimen prior to April 2018. Two consecutive negative cultures collected > 15 days apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups.

FINDINGS
1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%) or both (10%). Of these, 939 (85%) experienced culture conversion within six months. In adjusted analyses, patients with HIV had a lower probability of conversion (0·73 [95% CI: 0·62, 0·84]) than patients without HIV (0·84 [95% CI: 0·79, 0·90]; p=0·03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0·68 [95% CI: 0·57, 0·79]) relative to patients without either (0·89; 95% CI: 0·84, 0·95; p=0·0004). Hepatitis C infection, diabetes mellitus/glucose intolerance, and baseline resistance were not associated with conversion.

INTERPRETATION
Frequent sputum conversion in patients with rifampin-resistant/MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease.
Countries
GeorgiaKazakhstanLesothoPakistanPeruSouth AfricaIndia
Subject Area
antibiotic resistancetuberculosisantimicrobial resistance
Collections
The endTB project
DOI
10.1164/rccm.202001-0135OC
Published Date
24-Jul-2020
PubMed ID
32706644
Languages
English
Journal
American Journal of Respiratory and Critical Care Medicine
Volume / Issue / Pages
Volume 203, Issue 1, Pages 111-119
Issue Date
01-Jan-2021
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