Discrepant Results Between Pyrazinamide Susceptibility Testing by the Reference BACTEC 460TB Method andpncADNA Sequencing in Patients Infected With Multidrug-Resistant W-BeijingMycobacterium tuberculosisStrains

Background: Mycobacterium tuberculosisstrains 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 thepncAgene.Results:We found that despite of the presence of a strain W-specific Thr47Ala in thepncAgene, 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 thepncAgene for resistance-associated mutations.