Characteristics of pncA mutations in multidrug-resistant tuberculosis in Taiwan

MDRTB isolates were collected from six hospitals in Taiwan from January 2007 to December 2009. pncA 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 pncA gene analysis were estimated based on the results of PZA susceptibility testing.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 pncA gene, and most of them were point mutations. The sensitivities of pncA 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.More than half of the MDRTB isolates in this study are PZA-resistant. Analysis of pncA gene mutations helped to identify PZA-susceptible MDRTB isolates, especially in non-Beijing strains.Despite the recent advances in management, tuberculosis (TB) remains a leading cause of mortality and morbidity worldwide. The emergence of multidrug-resistant tuberculosis (MDRTB) further constitutes a serious threat to the control of TB. In Taiwan, the incidence of TB was 63.2/100,000 population in 2007 and 62.0/100,000 population in 2008 (1). The Taiwan drug resistance surveillance program revealed that the combined drug resistance rates in 2005 were 10.1% for isoniazid (INH), 6.2% for rifampicin (RIF), and 4.0% for MDRTB (2). Among the various genotypes of Mycobacterium tuberculosis (MTB), the Beijing genotype is the dominant strain in Taiwan (3, 4).Pyrazinamide (PZA) is an important first-line anti-tuberculosis (anti-TB) drug that is used in short-course