title: Discrepant results between pyrazinamide susceptibility testing by the reference BACTEC 460TB method and pncA DNA sequencing in patients infected with multidrug-resistant W-Beijing Mycobacterium tuberculosis strains.
abstract: BACKGROUND
  Mycobacterium tuberculosis strains belonging to the W-Beijing family have received broad clinical and public health attention because of their rapid worldwide spread and their frequent association with outbreaks, multidrug resistance, and treatment failures and relapses.
  
  
  METHODS
  The present study examined a large number of multidrug-resistant strain-W isolates (isolates of 29 patients) by susceptibility testing for pyrazinamide (PZA) using the reference BACTEC 460TB method (Becton Dickinson Diagnostic Instrument Systems; Sparks, MD) and also by DNA sequencing of the pncA gene.
  
  
  RESULTS
  We found that despite of the presence of a strain W-specific Thr47Ala in the pncA gene, all strains showed susceptibility to PZA in the reference BACTEC 460TB system due to their higher minimum inhibitory concentrations (relative to BACTEC 460TB PZA-susceptible strains).
  
  
  CONCLUSIONS
  Our results suggest that the current radiometric reference method cannot reproducibly detect PZA resistance in patients infected with W-Beijing strains. Therefore, PZA susceptibility testing should instead be based on analysis of the pncA gene for resistance-associated mutations.
authors.affiliation: Wadsworth Center, New York State Department of Health, PO Box 509, Albany, NY 12201-0509, USA.
authors.forename: Jillian
authors.initials: J
authors.lastname: Dormandy
authors.forename: Akos
authors.initials: A
authors.lastname: Somoskovi
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Driscoll
authors.forename: David
authors.initials: D
authors.lastname: Ashkin
authors.forename: Max
authors.initials: M
authors.lastname: Salfinger
mesh_terms: D000581:Amidohydrolases / Q000235:genetics*; D000995:Antitubercular Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D011718:Pyrazinamide / Q000494:pharmacology*; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D000581:Amidohydrolases; C487496:PncA protein, Mycobacterium tuberculosis