Conţinutul numărului revistei |
Articolul precedent |
Articolul urmator |
337 0 |
SM ISO690:2012 CHESOV, Elena, CHESOV, Dumitru, MAURER, Florian P., ANDRES, Sonke, UTPATEL, Christian, BARILAR, Ivan, DONICA, Ana, REIMANN , Maja, NIEMANN, Stefan, LANGE, Christoph G., KRUDU, V., HEYCKENDORF, Jan, MERKER, Matthias. Emergence of bedaquiline resistance in a high tuberculosis burden country. In: European Respiratory Journal, 2022, vol. 59, pp. 1-10. ISSN 0903-1936. DOI: https://doi.org/10.1183/13993003.00621-2021 |
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European Respiratory Journal | |
Volumul 59 / 2022 / ISSN 0903-1936 /ISSNe 1399-3003 | |
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DOI:https://doi.org/10.1183/13993003.00621-2021 | |
Pag. 1-10 | |
Rezumat | |
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 out of 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, four (15.3%) patients harboured strains which acquired bedaquiline resistance under therapy, while one (3.8%) patient 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 (OR 1.92 per unit increase, 95% CI 1.15–3.21; p=0.012). 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. |
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Cuvinte-cheie Antitubercular Agents, Cross-Sectional Studies, Diarylquinolines, Humans, Mycobacterium tuberculosis, tuberculosis, tuberculosis, Multidrug-Resistant |
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