Emergence of bedaquiline resistance in a high tuberculosis burden country
Open Access
- 9 September 2021
- journal article
- research article
- Published by European Respiratory Society (ERS) in European Respiratory Journal
- Vol. 59 (3), 2100621
- https://doi.org/10.1183/13993003.00621-2021
Abstract
Rationale Bedaquiline has been classified as a Group A drug for the treatment of multidrug-resistant tuberculosis (MDR-TB) by the World Health Organization, however globally emerging resistance threatens the effectivity of novel MDR-TB treatment regimens. Objectives We analysed pre-existing and emerging bedaquiline resistance in bedaquiline-based MDR-TB therapies, and risk factors associated with treatment failure and death. Methods In a cross-sectional cohort study, we employed patient data, whole genome sequencing (WGS) and phenotyping of Mycobacterium tuberculosis complex (MTBC) isolates. We could retrieve baseline isolates from 30.5% (62/203) of all MDR-TB patients who received bedaquiline between 2016 and 2018 in the Republic of Moldova. This includes 26 patients for whom we could also retrieve a follow-up isolate. Measurements and Main Results At baseline, all MTBC isolates were susceptible to bedaquiline. Among 26 patients with available baseline and follow-up isolates, 4/26 (15.3%) patients harbored strains which acquired bedaquiline resistance under therapy, while 1/26 (3.8%) patients was re-infected with a second bedaquiline resistant strain. Treatment failure and death were associated with cavitary disease (p=0.011), and any additional drug prescribed in the bedaquiline containing regimen with WGS-predicted resistance at baseline (p=0.012, OR 1.92 per unit increase, 95%CI 1.15–3.21). Conclusions MDR-TB treatments based on bedaquiline require a functional background regimen to achieve high cure rates and to prevent the evolution of bedaquiline resistance. Novel MDR-TB therapies with bedaquiline require timely and comprehensive drug resistance monitoring.Keywords
Funding Information
- Deutsches Zentrum für Infektionsforschung
- German Excellence cluster Precision Medicine in Inflammation (EXC 2167)
- Common Action against HIV/TB/HCV across the Regions of Europe (825673)
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