WFRF:(Maurer Florian P.)
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Emergence of bedaquiline resistance in a high tuberculosis burden country
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- Chesov, Elena (författare)
- Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova; Chiril Draganiuc Phthisiopneumology Institute, Chisinau, Moldova; German Centre for Infection Research (DZIF), Partner site Hamburg-Lübeck-Borstel-Riems, Germany; Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
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- Chesov, Dumitru (författare)
- Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova; German Centre for Infection Research (DZIF), Partner site Hamburg-Lübeck-Borstel-Riems, Germany; Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
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- Maurer, Florian P. (författare)
- National and Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany; Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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- 2021-09-09
- 2022
- Engelska.
- Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 59:3
- Tidskriftsartikel (refereegranskat)
Abstract
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
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