title: Redefining MTBDRplus test results: what do indeterminate results actually mean?
abstract: BACKGROUND
  Although line-probe assays (LPAs) are promising, little research has been conducted to elucidate the true nature of indeterminate LPA results or assess the ability of these assays to perform on a wide range of clinical samples.
  
  
  OBJECTIVE
  To evaluate the performance of the commercially available GenoType(®) MTBDRplus LPA against conventional BACTEC™ MGIT™ 960 culture and drug susceptibility testing (DST) among 308 pulmonary tuberculosis (PTB) and 32 extra-pulmonary TB samples.
  
  
  RESULTS
  Invalid LPA results (defined as those with a missing Mycobacterium tuberculosis identification band) were obtained for 18 PTB samples, which were excluded from further analysis. The sensitivity and specificity of the MTBDRplus assay for multidrug-resistant TB, based upon the results obtained for the remaining 322 samples, was respectively 95.2% and 95.1%. Of 290 PTB samples, 40 (13.7%) were indeterminate on LPA (defined as the absence of both wild-type and corresponding mutation bands) for isoniazid (INH) and/or rifampicin (RMP), and were further evaluated by pyrosequencing (PSQ). Contrary to standard LPA interpretation, INH and RMP susceptibility were confirmed by both DST and PSQ in respectively 7.5% (3/40) and 27.5% (11/40) of indeterminate samples.
  
  
  CONCLUSIONS
  PSQ was found to be a valuable and rapid technique to resolve discrepancies in LPA test results that were not interpretable.
authors.affiliation: Department of Microbiology, P D Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: C
authors.initials: C
authors.lastname: Nikam
authors.affiliation: Department of Microbiology, P D Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: R
authors.initials: R
authors.lastname: Patel
authors.affiliation: Department of Microbiology, P D Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: M
authors.initials: M
authors.lastname: Sadani
authors.affiliation: Department of Microbiology, P D Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: K
authors.initials: K
authors.lastname: Ajbani
authors.affiliation: Department of Microbiology, P D Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: M
authors.initials: M
authors.lastname: Kazi
authors.affiliation: Department of Microbiology, P D Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: R
authors.initials: R
authors.lastname: Soman
authors.affiliation: Department of Microbiology, P D Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: A
authors.initials: A
authors.lastname: Shetty
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Georghiou
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Rodwell
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California, USA.
authors.forename: A
authors.initials: A
authors.lastname: Catanzaro
authors.affiliation: Department of Microbiology, P D Hinduja Hospital and Medical Research Centre, Mumbai, India.
authors.forename: C
authors.initials: C
authors.lastname: Rodrigues
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D001431:Bacteriological Techniques; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial