Original article
Evaluation of whole genome sequencing and software tools for drug susceptibility testing of Mycobacterium tuberculosis

https://doi.org/10.1016/j.cmi.2018.03.041Get rights and content
Under an Elsevier user license
open archive

Abstract

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 €26 and €143 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.

Keywords

Drug resistance
Drug susceptibility testing
Evaluation
Mycobacterium tuberculosis
Whole genome sequencing

Cited by (0)

Presented in part at the Annual Congress of the European Society of Mycobacteriology, Šibenik, Croatia, June 2017; and at the European Scientific Conference on Applied Infectious Disease Epidemiology, Stockholm, Sweden, November 2017.