Pyrazinamide Resistance and Mutation Patterns Among Multidrug-Resistant Mycobacterium tuberculosis from Henan Province
| Autor: | Ruyue Su, Yankun Zhu, Danwei Zheng, Hui Li, Xiaoguang Ma, Ding-yong Sun, Jie Shi, Shaohua Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pharmacology Genetics Point mutation 030106 microbiology Pyrazinamide Biology biology.organism_classification Multiple drug resistance Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Infectious Diseases PncA Genotype medicine Culture conversion Pharmacology (medical) Multidrug-Resistant Mycobacterium tuberculosis 030212 general & internal medicine medicine.drug |
| Zdroj: | Infection and Drug Resistance. 13:2929-2941 |
| ISSN: | 1178-6973 |
| DOI: | 10.2147/idr.s260161 |
| Popis: | Purpose 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 first-line 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 PZA-resistant 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. |
| Databáze: | OpenAIRE |
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