A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia

PLoS One. 2016 Nov 30;11(11):e0167093. doi: 10.1371/journal.pone.0167093. eCollection 2016.

Abstract

Background: The goal of this study was to compare the consistency of three assays for the determination of the drug resistance of Mycobacterium tuberculosis (MTB) strains with various resistance profiles isolated from the Moscow region.

Methods: A total of 144 MTB clinical isolates with a strong bias toward drug resistance were examined using Bactec MGIT 960, Sensititre MycoTB, and a microarray-based molecular assay TB-TEST to detect substitutions in the rpoB, katG, inhA, ahpC, gyrA, gyrB, rrs, eis, and embB genes that are associated with resistance to rifampin, isoniazid, fluoroquinolones, second-line injectable drugs and ethambutol.

Results: The average correlation for the identification of resistant and susceptible isolates using the three methods was approximately 94%. An association of mutations detected with variable resistance levels was shown. We propose a change in the breakpoint minimal inhibitory concentration for kanamycin to less than 5 μg/ml in the Sensititre MycoTB system. A pairwise comparison of the minimal inhibitory concentrations (MICs) of two different drugs revealed an increased correlation in the first-line drug group and a partial correlation in the second-line drug group, reflecting the history of the preferential simultaneous use of drugs from these groups. An increased correlation with the MICs was also observed for drugs sharing common resistance mechanisms.

Conclusions: The quantitative measures of phenotypic drug resistance produced by the Sensititre MycoTB and the timely detection of mutations using the TB-TEST assay provide guidance for clinicians for the choice of the appropriate drug regimen.

Publication types

  • Comparative Study

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / therapeutic use
  • Drug Resistance, Bacterial / genetics*
  • Genotype
  • Humans
  • Microbial Sensitivity Tests / methods*
  • Moscow
  • Mutation
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification
  • Mycobacterium tuberculosis / physiology
  • Oligonucleotide Array Sequence Analysis*
  • Phenotype
  • Tuberculosis / drug therapy

Substances

  • Antitubercular Agents

Grants and funding

This work was supported by the Russian Science Foundation (grant no. 14-50-00060).