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.
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: Molly F Franke; Mercedes C Becerra; Dylan B Tierney; Michael L Rich; Cesar Bonilla; Jaime Bayona; Megan M McLaughlin; Carole D Mitnick Journal: Ann Am Thorac Soc Date: 2015-05
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Authors: Gustavo E Velásquez; Roger I Calderon; Carole D Mitnick; Mercedes C Becerra; Chuan-Chin Huang; Zibiao Zhang; Carmen C Contreras; Rosa M Yataco; Jerome T Galea; Leonid W Lecca; Megan B Murray Journal: Antimicrob Agents Chemother Date: 2016-10-21 Impact factor: 5.191
Authors: Glenn P Morlock; Frances C Tyrrell; Dorothy Baynham; Vincent E Escuyer; Nicole Green; Youngmi Kim; Patricia A Longley-Olson; Nicole Parrish; Courtney Pennington; Desmond Tan; Brett Austin; James E Posey Journal: Tuberc Res Treat Date: 2017-11-08