<p>Pyrazinamide Resistance and Mutation Patterns Among Multidrug-Resistant <em>Mycobacterium tuberculosis</em> from Henan Province</p>

Abstract

This study was designed to identify the phenotypic and genotypic characteristics of pyrazinamide (PZA) resistance among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) from Henan and to evaluate the efficacy of pncA, rpsA, and panD mutations in predicting PZA resistance. Materials and Methods: A total of 152 MDR strains were included in this study. The Bactec MGIT system was used to determine PZA susceptibility for all strains. The pncA, rpsA, and panD genes were sequenced to identify any mutations, and the sequences were then aligned with the sequence of standard strain H37Rv. Moreover, the correlations between PZA-resistant phenotypes and treatment outcomes were analysed. Results: Of the152 strains, 105 had a PZA-resistant phenotype, and 102 harboured the pncA mutation. The PZA resistance rate was higher in the strains with resistance to all four firstline drugs and those that were pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR). A total of 100 different pncA mutation patterns were identified, including 80 point mutations and 20 insertions/deletions, and 32 new pncA mutation patterns were detected. In this study, 13 strains had multiple mutations. Of the11 PZA-resistant strains without pncA mutations, two harboured the rpsA mutation, and one harboured the panD mutation. With PZA susceptibility results as the reference, single-gene pncA sequencing had sensitivity of 89.52% and specificity of 89.36%. With the combination of rpsA and panD, the sensitivity increased to 92.38%, and the specificity remained the same. No significant differences were observed in the sputum smear/culture conversion rate between PZAresistant patients and PZA-sensitive patients. However, PZA resistance was related to the time to sputum smear/culture conversion (P = 0.018). Conclusion: The combination of pncA, rpsA, and panD was beneficial for the timely diagnosis of PZA resistance and could provide a laboratory basis for customizing treatment regimens for MDR-TB patients.

Comparative Performance of Genomic Methods for the Detection of Pyrazinamide Resistance and Heteroresistance in Mycobacterium tuberculosis

“…Fourteen isolates (3.9%) had discrepant genotype-phenotype results for PZA susceptibility. Several studies have described a small minority of isolates as phenotypically resistant without an observed pncA variant ( 44 , 45 , 48 – 50 ). Previous investigators have attributed this false-positive resistance to the technical challenges associated with phenotypic DST or to another mechanism of resistance (e.g., resistance-associated variants in panD , rpsA , and clpC1 ).…”

Treatment Outcomes and Risk Factors of Multidrug-Resistant Tuberculosis Patients in Xi’an China, a Retrospective Cohort Study

“…29 However, some studies have shown that when pyrazinamide is sensitive, it can help with early smear conversion and improve treatment success rates. 30,31 As a result, if enough core drugs from Groups A and B were not selected, pyrazinamide can be used.…”

Quantitative MODS-Wayne Assay for Rapid Detection of Pyrazinamide Resistance inMycobacterium tuberculosisfrom Sputum Samples

“…Enzymatic activity alone accounts for only 27.3% of PZA resistance cases [39], while the POA efflux rate contributes to around 51% [41]. Notably, 70-90% of PZA-resistant strains show mutations in the pncA gene and its promoter region [43]- [45]. This suggests that a significant portion of resistant strains may involve other, yet unidentified, mechanisms contributing to PZA resistance.…”