Performance of GenoType MTBDRsl assay for detection of second-line drugs and ethambutol resistance directly from sputum specimens of MDR-TB patients in Bangladesh

PLoS One. 2021 Dec 16;16(12):e0261329. doi: 10.1371/journal.pone.0261329. eCollection 2021.

Abstract

Background: Rapid and early detection of drug susceptibility among multidrug-resistant tuberculosis (MDR-TB) patients could guide the timely initiation of effective treatment and reduce transmission of drug-resistant TB. In the current study, we evaluated the diagnostic performance of GenoType MTBDRsl (MTBDRsl) ver1.0 assay for detection of resistance to ofloxacin (OFL), kanamycin (KAN) and ethambutol (EMB), and additionally the XDR-TB among MDR-TB patients in Bangladesh.

Methods: The MTBDRsl assay was performed directly on 218 smear-positive sputum specimens collected from MDR-TB patients and the results were compared with the phenotypic drug susceptibility testing (DST) performed on solid Lowenstein-Jensen (L-J) media. We also analyzed the mutation patterns of gyrA, rrs, and embB genes for detection of resistance to OFL, KAN and EMB, respectively.

Results: The sensitivity and specificity of the MTBDRsl compared to phenotypic L-J DST were 81.8% (95% CI, 69.1-90.9) and 98.8% (95% CI, 95.6-99.8), respectively for OFL (PPV: 95.7% & NPV: 94.1%); 65.1% (95% CI, 57.5-72.2) and 86.7% (95% CI, 73.2-94.9), respectively for EMB (PPV: 94.9% & NPV: 39.4%); and 100% for KAN. The diagnostic accuracy of KAN, OFL and EMB were 100, 94.5 and 69.6%, respectively. Moreover, the sensitivity, specificity and diagnostic accuracy of MtBDRsl for detection of XDR-TB was 100%. The most frequently observed mutations were at codon D94G (46.8%) of gyrA gene, A1401G (83.3%) of rrs gene, and M306V (41.5%) of the embB gene.

Conclusion: Considering the excellent performance in this study we suggest that MTBDRsl assay can be used as an initial rapid test for detection of KAN and OFL susceptibility, as well as XDR-TB directly from smear-positive sputum specimens of MDR-TB patients in Bangladesh.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antitubercular Agents / therapeutic use
  • Bangladesh / epidemiology
  • DNA, Bacterial / genetics
  • Ethambutol / therapeutic use
  • Extensively Drug-Resistant Tuberculosis / diagnosis
  • Extensively Drug-Resistant Tuberculosis / drug therapy
  • Extensively Drug-Resistant Tuberculosis / genetics
  • Female
  • Genotype
  • Genotyping Techniques / methods
  • Humans
  • Kanamycin / therapeutic use
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mycobacterium tuberculosis / genetics*
  • Ofloxacin / therapeutic use
  • Sensitivity and Specificity
  • Sputum / chemistry
  • Tuberculosis, Multidrug-Resistant / diagnosis*
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / genetics*

Substances

  • Antitubercular Agents
  • DNA, Bacterial
  • Kanamycin
  • Ethambutol
  • Ofloxacin

Grants and funding

This research was funded by USAID through CDC, grant number: 5U01CI000628. icddr,b acknowledges with gratitude the commitment of USAID and CDC to its research efforts. icddr,b is also grateful to the Governments of Bangladesh, Canada, Sweden and the UK for providing core/unrestricted support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.