Journal
CLINICAL MICROBIOLOGY AND INFECTION
Volume 25, Issue 1, Pages 82-86Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.cmi.2018.03.041
Keywords
Drug resistance; Drug susceptibility testing; Evaluation; Mycobacterium tuberculosis; Whole genome sequencing
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Funding
- Tampere Tuberculosis Foundation
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Objectives: Culture-based assays are currently the reference standard for drug susceptibility testing for Mycobacterium tuberculosis. They provide good sensitivity and specificity but are time consuming. The objective of this study was to evaluate whether whole genome sequencing (WGS), combined with software tools for data analysis, can replace routine culture-based assays for drug susceptibility testing of M. tuberculosis. Methods: M. tuberculosis cultures sent to the Finnish mycobacterial reference laboratory in 2014 (n = 211) were phenotypically tested by Mycobacteria Growth Indicator Tube (MGIT) for first-line drug susceptibilities. WGS was performed for all isolates using the Illumina MiSeq system, and data were analysed using five software tools (PhyResSE, Mykrobe Predictor, TB Profiler, TGS-TB and KvarQ). Diagnostic time and reagent costs were estimated for both methods. Results: The sensitivity of the five software tools to predict any resistance among strains was almost identical, ranging from 74% to 80%, and specificity was more than 95% for all software tools except for TGS-TB. The sensitivity and specificity to predict resistance to individual drugs varied considerably among the software tools. Reagent costs for MGIT and WGS were V26 and V143 per isolate respectively. Turnaround time for MGIT was 19 days (range 10-50 days) for first-line drugs, and turnaround time for WGS was estimated to be 5 days (range 3-7 days). Conclusions: WGS could be used as a prescreening assay for drug susceptibility testing with confirmation of resistant strains by MGIT. The functionality and ease of use of the software tools need to be improved. (C) 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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