title: Rapid detection of drug resistance and mutational patterns of extensively drug-resistant strains by a novel GenoType® MTBDRsl assay.
abstract: BACKGROUND
  The emergence of extensively drug-resistant tuberculosis (XDR-TB) is a major concern in the India. The burden of XDR-TB is increasing due to inadequate monitoring, lack of proper diagnosis, and treatment. The GenoType ® Mycobacterium tuberculosis drug resistance second line (MTBDRsl) assay is a novel line probe assay used for the rapid detection of mutational patterns conferring resistance to XDR-TB.
  
  
  OBJECTIVE
  The aim of this study was to study the rapid detection of drug resistance and mutational patterns of the XDR-TB by a novel GenoType ® MTBDRsl assay.
  
  
  METHODS
  We evaluated 98 multidrug-resistant (MDR) M. tuberculosis isolates for second line drugs susceptibility testing by 1% proportion method (BacT/ALERT 3D system) and GenoType ® MTBDRsl assay for rapid detection of conferring drug resistance to XDR-TB.
  
  
  RESULTS
  A total of seven (17.4%) were identified as XDR-TB by using standard phenotypic method. The concordance between phenotypic and GenoType ® MTBDRsl assay was 91.7-100% for different antibiotics. The sensitivity and specificity of the MTBDRsl assay were 100% and 100% for aminoglycosides; 100% and 100% for fluoroquinolones; 91.7% and 100% for ethambutol. The most frequent mutations and patterns were gyrA MUT1 (A90V) in seven (41.2%) and gyrA + WT1-3 + MUT1 in four (23.5%); rrs MUT1 (A1401G) in 11 (64.7%), and rrs WT1-2 + MUT1 in eight (47.1%); and embB MUT1B (M306V) in 11 (64.7%) strains.
  
  
  CONCLUSIONS
  These data suggest that the GenoType ® MTBDRsl assay is rapid, novel test for detection of resistance to second line anti-tubercular drugs. This assay provides additional information about the frequency and mutational patterns responsible for XDR-TB resistance.
authors.affiliation: Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Singh
authors.forename: A K
authors.initials: AK
authors.lastname: Maurya
authors.forename: S
authors.initials: S
authors.lastname: Kant
authors.forename: J
authors.initials: J
authors.lastname: Umrao
authors.forename: R A S
authors.initials: RA
authors.lastname: Kushwaha
authors.forename: V L
authors.initials: VL
authors.lastname: Nag
authors.forename: T N
authors.initials: TN
authors.lastname: Dhole
mesh_terms: D000583:Amikacin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D027081:DNA Gyrase / Q000235:genetics; D004977:Ethambutol / Q000627:therapeutic use; D054908:Extensively Drug-Resistant Tuberculosis / Q000175:diagnosis / Q000188:drug therapy*; D024841:Fluoroquinolones / Q000627:therapeutic use; D060005:Genotyping Techniques; D006801:Humans; D007612:Kanamycin / Q000627:therapeutic use; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification*; D010430:Pentosyltransferases / Q000235:genetics; D010641:Phenotype; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012680:Sensitivity and Specificity
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D012336:RNA, Ribosomal, 16S; D007612:Kanamycin; D000583:Amikacin; D004977:Ethambutol; C540269:EmbB protein, Mycobacterium tuberculosis; D010430:Pentosyltransferases; D027081:DNA Gyrase