Abstract

<p>Abstract</p> <p>Background</p> <p>Pyrazinamide (PZA) is an important first-line drug in multidrug-resistant tuberculosis (MDRTB) treatment. However, the unreliable results obtained from traditional susceptibility testing limits its usefulness in clinical settings. The detection of <it>pncA </it>gene mutations is a potential surrogate of PZA susceptibility testing, especially in MDRTB isolates. The impact of genotypes of <it>M. tuberculosis </it>in <it>pncA </it>gene mutations also remains to be clarified.</p> <p>Methods</p> <p>MDRTB isolates were collected from six hospitals in Taiwan from January 2007 to December 2009. <it>pncA </it>gene sequencing, pyrazinamidase activity testing, and spoligotyping were performed on all of the isolates. PZA susceptibility was determined by the BACTEC MGIT 960 PZA method. The sensitivity and specificity of <it>pncA </it>gene analysis were estimated based on the results of PZA susceptibility testing.</p> <p>Results</p> <p>A total of 66 MDRTB isolates, including 37 Beijing and 29 non-Beijing strains, were included for analysis. Among these isolates, 36 (54.5%) were PZA-resistant and 30 (45.5%) were PZA-susceptible. The PZA-resistant isolates were more likely to have concomitant resistance to ethambutol and streptomycin. Thirty-seven mutation types out of 30 isolates were identified in the <it>pncA </it>gene, and most of them were point mutations. The sensitivities of <it>pncA </it>gene sequencing for PZA susceptibility in overall isolates, Beijing and non-Beijing strains were 80.6%, 76.2%, and 86.7% respectively, and the specificities were 96.7%, 93.8%, and 100% respectively.</p> <p>Conclusions</p> <p>More than half of the MDRTB isolates in this study are PZA-resistant. Analysis of <it>pncA </it>gene mutations helped to identify PZA-susceptible MDRTB isolates, especially in non-Beijing strains.</p

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