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doi:10.1378/chest.06-1899
(Chest. 2007; 131:497-501)
© 2007 American College of Chest Physicians
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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*

Jillian Dormandy, BS; Akos Somoskovi, MD, PhD; Barry N. Kreiswirth, PhD; Jeffrey R. Driscoll, PhD; David Ashkin, MD and Max Salfinger, MD

* From the Wadsworth Center (Drs. Somoskovi, Driscoll, and Salfinger and Ms. Dormandy), New York State Department of Health, Albany, NY; Public Health Research Institute (Dr. Kreiswirth), Newark, NJ; and A.G. Holley State Hospital (Dr. Ashkin), Lantana, FL.

Correspondence to: Max Salfinger, MD, Wadsworth Center, New York State Department of Health, PO Box 509, Albany, NY 12201-0509; e-mail: salfinger{at}wadsworth.org

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.

Key Words: multidrug resistant • Mycobacterium tuberculosis • pncA • pyrazinamide • susceptibility testing • tuberculosis • W-Beijing genotype






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