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 |
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| Authors: | Dormandy Jillian Somoskovi Akos Kreiswirth Barry N Driscoll Jeffrey R Ashkin David Salfinger Max |
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| Affiliation: | Wadsworth Center, New York State Department of Health, PO Box 509, Albany, NY 12201-0509, USA. |
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| 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. |
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| Keywords: | multidrug resistant pyrazinamide susceptibility testing tuberculosis W-Beijing genotype INH" },{" #name" :" keyword" ," $" :{" id" :" cekeyw81" }," $$" :[{" #name" :" text" ," _" :" isoniazid MDR" },{" #name" :" keyword" ," $" :{" id" :" cekeyw83" }," $$" :[{" #name" :" text" ," _" :" multidrug resistant MIC" },{" #name" :" keyword" ," $" :{" id" :" cekeyw85" }," $$" :[{" #name" :" text" ," _" :" minimal inhibitory concentration PZA" },{" #name" :" keyword" ," $" :{" id" :" cekeyw89" }," $$" :[{" #name" :" text" ," _" :" pyrazinamide PZase" },{" #name" :" keyword" ," $" :{" id" :" cekeyw91" }," $$" :[{" #name" :" text" ," _" :" pyrazinamidase RFLP" },{" #name" :" keyword" ," $" :{" id" :" cekeyw93" }," $$" :[{" #name" :" text" ," _" :" restriction fragment length polymorphism RIF" },{" #name" :" keyword" ," $" :{" id" :" cekeyw95" }," $$" :[{" #name" :" text" ," _" :" rifampin XDR" },{" #name" :" keyword" ," $" :{" id" :" cekeyw97" }," $$" :[{" #name" :" text" ," _" :" extensively drug resistant |
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