Validation of pncA Gene Sequencing in Combination with the Mycobacterial Growth Indicator Tube Method To Test Susceptibility of Mycobacterium tuberculosis to Pyrazinamide Sami O. Simons a , Jakko van Ingen a , Tridia van der Laan b , Arnout Mulder b , P. N. Richard Dekhuijzen a , Martin J. Boeree a and Dick van Soolingen b a Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands b National Institute for Public Health and the Environment, Bilthoven, the Netherlands ABSTRACT Pyrazinamide is important in the treatment of tuberculosis. Unfortunately, the diagnosis of pyrazinamide resistance is hampered by technical difficulties. We hypothesized that mutation analysis combined with the mycobacterial growth indicator tube (MGIT) phenotypic method would be a good predictor of pyrazinamide resistance. We prospectively analyzed 1,650 M. tuberculosis isolates referred to our tuberculosis reference laboratory in 2008 and 2009. In our laboratory, the MGIT 960 system was used for pyrazinamide resistance screening. If a pyrazinamide-resistant strain was detected, we performed a pncA gene mutation analysis. A second MGIT 960 susceptibility assay was performed afterwards to evaluate the accuracy of the pncA mutation analysis to detect true- or false-positive MGIT results. We observed pyrazinamide resistance in 69 samples using the first MGIT 960 analysis. In a second MGIT 960 analysis, 47 of the 69 samples proved susceptible (68% false positivity). Sensitivity of nonsynonymous pncA mutations for detecting resistant isolates was 73% (95% confidence interval (CI), 61% to 73%), and specificity was 100% (95% CI, 95% to 100%). A diagnostic algorithm incorporating phenotypic and molecular methods would have a 100% positive predictive value for detecting pyrazinamide-resistant isolates, indicating that such an algorithm, based on both methods, is a good predictor for pyrazinamide resistance in routine diagnostics.
Validation of pncA Gene Sequencing in Combination with the Mycobacterial Growth Indicator Tube Method To Test Susceptibility of Mycobacterium tuberculosis to Pyrazinamide
Abstract
Validation of pncA Gene Sequencing in Combination with the Mycobacterial Growth Indicator Tube Method To Test Susceptibility of Mycobacterium tuberculosis to Pyrazinamide Sami O. Simons a , Jakko van Ingen a , Tridia van der Laan b , Arnout Mulder b , P. N. Richard Dekhuijzen a , Martin J. Boeree a and Dick van Soolingen b a Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands b National Institute for Public Health and the Environment, Bilthoven, the Netherlands ABSTRACT Pyrazinamide is important in the treatment of tuberculosis. Unfortunately, the diagnosis of pyrazinamide resistance is hampered by technical difficulties. We hypothesized that mutation analysis combined with the mycobacterial growth indicator tube (MGIT) phenotypic method would be a good predictor of pyrazinamide resistance. We prospectively analyzed 1,650 M. tuberculosis isolates referred to our tuberculosis reference laboratory in 2008 and 2009. In our laboratory, the MGIT 960 system was used for pyrazinamide resistance screening. If a pyrazinamide-resistant strain was detected, we performed a pncA gene mutation analysis. A second MGIT 960 susceptibility assay was performed afterwards to evaluate the accuracy of the pncA mutation analysis to detect true- or false-positive MGIT results. We observed pyrazinamide resistance in 69 samples using the first MGIT 960 analysis. In a second MGIT 960 analysis, 47 of the 69 samples proved susceptible (68% false positivity). Sensitivity of nonsynonymous pncA mutations for detecting resistant isolates was 73% (95% confidence interval (CI), 61% to 73%), and specificity was 100% (95% CI, 95% to 100%). A diagnostic algorithm incorporating phenotypic and molecular methods would have a 100% positive predictive value for detecting pyrazinamide-resistant isolates, indicating that such an algorithm, based on both methods, is a good predictor for pyrazinamide resistance in routine diagnostics.Preview Only. This article cannot be rented because we do not currently have permission from the publisher.
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Validation of pncA Gene Sequencing in Combination with the Mycobacterial Growth Indicator Tube Method To Test Susceptibility of Mycobacterium tuberculosis to Pyrazinamide
Simons, Sami O.; van Ingen, Jakko; van der Laan, Tridia; Mulder, Arnout; Dekhuijzen, P. N. Richard; Boeree, Martin J.; van Soolingen, Dick
Follow Journal of Clinical Microbiology
, Volume 50 (2): 428
American Society For Microbiology – Feb 1, 2012
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