Phenotypic and Genotypic Characterization of Pyrazinamide Resistance among Multidrug-Resistant Mycobacterium tuberculosis Isolates in Zhejiang, China

Abstract

e To explore the phenotypic and genotypic characterization of pyrazinamide (PZA) resistance among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates in Zhejiang province, a total of 274 MDR-TB isolates were collected. Drug susceptibility testing and spoligotyping were performed on all clinical isolates. In addition, the mutated features of PZA-resistant loci, including pncA and rpsA, were also analyzed by DNA sequencing. Our results showed that the prevalence of PZA resistance among MDR-TB strains in Zhejiang province was 43.07% and that PZA resistance was associated with concomitant resistance to streptomycin. The majority of PZA-resistant MDR-TB isolates belonged to the Beijing family. Mutations within pncA, not rpsA, constituted the primary mechanism of PZA resistance. Among 118 PZA-resistant isolates, 53 different mutations were observed in pncA, and most of them were point mutations. Compared with the phenotypic data, DNA sequencing of pncA has sensitivity and specificity of 77.97% and 96.79%, respectively. Analysis of pncA provided a robust tool for rapid detection of PZA drug resistance.

Multicenter Study of the Emergence and Genetic Characteristics of Pyrazinamide-Resistant Tuberculosis in China

“…PZA susceptibility testing by Bactec MGIT 960 revealed that 16.7% (147/878) of the studied patients were PZA resistant. Simultaneously, a higher level of PZA resistance (30.2% [39/129]) was found in the MDR-TB isolates, which is consistent with previously reported studies with PZA resistance proportions ranging from 36% to 54% among MDR-TB patients (18)(19)(20). A significantly higher proportion of PZA resistance was observed in MDR cases than in first-line drugsusceptible cases (30.2% versus7.7%; P Ͻ 0.001).…”

“…In contrast to earlier hospital-based studies or those conducted in a single region in China (18), the present study was multicenter, to better understand the epidemiological situation of PZA resistance across China. This is the first reported population-based study of PZA resistance among TB cases in China.…”

Genotyping and Prevalence of Pyrazinamide- and Moxifloxacin-Resistant Tuberculosis in China, 2000 to 2010

“…In addition, it should be noted that the proportion of MDR tuberculosis with PZA resistance has reached 50.0% (versus 11.3% in non-MDR TB) in China, which is consistent with a report from Zhejiang Province in China (43.1%) (32). Numerous lines of evidence demonstrate that MDR-TB is more likely to acquire resistance to PZA, which may be correlated with a higher frequency of developing pncA mutations conferring PZA resistance after the acquisition of both RIF and INH resistance (33).…”

pncA Gene Mutations Associated with Pyrazinamide Resistance in Drug-Resistant Tuberculosis, South Africa and Georgia

“…Given the high likelihood of frameshift mutations resulting in resistance and the high specificity (94%–98%) of pncA SNPs for pyrazinamide resistance ( 13 , 14 ), we estimate that at least 56%–66% of MDR TB and 90%–95% of XDR TB cases from these settings are likely to be resistant to pyrazinamide. Only a small number of mutations were synonymous, previously associated with pyrazinamide susceptibility, or had an SNP for which phenotypic susceptibility has not been previously tested.…”