Underestimation of the resistance of Mycobacterium tuberculosis to second-line drugs by the new GenoType MTBDRsl test

J Mol Diagn. 2013 Jan;15(1):44-50. doi: 10.1016/j.jmoldx.2012.08.004. Epub 2012 Nov 15.

Abstract

The GenoType MTBDRsl is a new-generation PCR-based line-probe assay for the detection of extensively drug-resistant tuberculosis (XDR-TB). This study evaluated the performance of MTBDRsl in detecting genotypic resistance to ethambutol, kanamycin, and ofloxacin in Mycobacterium tuberculosis (MTB) strains. The drug resistance of 262 unique clinical MTB isolates from China was analyzed with MTBDRsl, traditional TB drug susceptibility testing (DST), and sequencing. Sensitivity of MTBDRsl was 62.4% (93/149; 95% CI = 54.1 to 70.2) for detection of ethambutol resistance, 57.9% (55/95; 95% CI = 47.3 to 68) for kanamycin resistance, and 81% (111/137; 95% CI = 73.4 to 87.2) for ofloxacin resistance; specificity was 76.8% (86/112; 95% CI = 67.9 to 84.2), 98.8% (164/166; 95% CI = 95.7 to 99.9), and 91.1% (113/124; 95% CI = 84.7 to 95.5), respectively. Sequencing suggested that 36.9% (55/149) of ethambutol-resistant strains had no embB306 mutation and that 26.8% (40/149) had embB497 mutation not covered by MTBDRsl. Furthermore, MTBDRsl indicated ethambutol resistance in 23.2% (26/112) of ethambutol-susceptible strains, of which 92.3% (24/26) were confirmed resistant by sequencing. This study demonstrated that genotypic resistance to ethambutol, kanamycin, and ofloxacin in MTB can be quickly determined with the MTBDRsl. As a rapid and convenient genetic method, this assay could function as a supplement to traditional DST. More relevant genetic markers are needed to improve sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology
  • China
  • DNA, Bacterial / genetics
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Ethambutol / pharmacology
  • Extensively Drug-Resistant Tuberculosis / diagnosis
  • Genotype
  • Humans
  • Kanamycin / pharmacology
  • Kanamycin Resistance / genetics
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification
  • Ofloxacin / pharmacology
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Analysis, DNA

Substances

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