Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China
Abstract Background Pyrazinamide still may be a useful drug for treatment of rifampin-resistant (RR-TB) or multidrug-resistant tuberculosis (MDR-TB) in China while awaiting scale up of new drugs and regimens including bedaquiline and linezolid. The level of pyrazinamide resistance among MDR-TB patie...
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| Format: | Article |
| Language: | English |
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BMC
2020-01-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-020-4758-9 |
| _version_ | 1819330583963107328 |
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| author | Hui Xia Susan van den Hof Frank Cobelens Yang Zhou Bing Zhao Shengfen Wang Yanlin Zhao |
| author_facet | Hui Xia Susan van den Hof Frank Cobelens Yang Zhou Bing Zhao Shengfen Wang Yanlin Zhao |
| author_sort | Hui Xia |
| collection | DOAJ |
| description | Abstract Background Pyrazinamide still may be a useful drug for treatment of rifampin-resistant (RR-TB) or multidrug-resistant tuberculosis (MDR-TB) in China while awaiting scale up of new drugs and regimens including bedaquiline and linezolid. The level of pyrazinamide resistance among MDR-TB patients in China is not well established. Therefore, we assessed pyrazinamide resistance in a representative sample and explored determinants and patterns of pncA mutations. Methods MDR-TB isolates from the 2007 national drug resistance survey of China were sub-cultured and examined for pyrazinamide susceptibility by BACTEC MGIT 960 method. pncA mutations were identified by sequencing. Characteristics associated with pyrazinamide resistance were analyzed using univariable and multivariable log-binominal regression. Results Of 401 MDR-TB isolates, 324 were successfully sub-cultured and underwent drug susceptibility testing. Pyrazinamide resistance was prevalent in 40.7% of samples, similarly among new and previously treated MDR-TB patients. Pyrazinamide resistance in MDR-TB patients was associated with lower age (adjusted OR 0.54; 95% CI, 0.34–0.87 for those aged ≧60 years compared to < 40 years). Pyrazinamide resistance was not associated with gender, residential area, previous treatment history and Beijing genotype. Of 132 patients with pyrazinamide resistant MDR-TB, 97 (73.5%) had a mutation in the pncA gene; with 61 different point mutations causing amino acid change, and 11 frameshifts in the pncA gene. The mutations were scattered throughout the whole pncA gene and no hot spot region was identified. Conclusions Pyrazinamide resistance among MDR-TB patients in China is common, although less so in elderly patients. Therefore, pyrazinamide should only be used for treatment of RR/MDR-TB in China if susceptibility is confirmed. Molecular testing for detection of pyrazinamide resistance only based on pncA mutations has certain value for the rapid detection of pyrazinamide resistance in MDR-TB strains but other gene mutations conferring to pyrazinamide resistance still need to be explored to increase its predictive ability . |
| first_indexed | 2024-12-24T14:00:50Z |
| format | Article |
| id | doaj.art-8e4fb74ce8fe4ba6b8a67e62654fdb50 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-24T14:00:50Z |
| publishDate | 2020-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-8e4fb74ce8fe4ba6b8a67e62654fdb502022-12-21T16:52:28ZengBMCBMC Infectious Diseases1471-23342020-01-0120111010.1186/s12879-020-4758-9Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in ChinaHui Xia0Susan van den Hof1Frank Cobelens2Yang Zhou3Bing Zhao4Shengfen Wang5Yanlin Zhao6National Tuberculosis Reference Laboratory, National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and PreventionKNCV Tuberculosis FoundationDepartment of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam University Medical CentersNational Tuberculosis Reference Laboratory, National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and PreventionNational Tuberculosis Reference Laboratory, National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and PreventionNational Tuberculosis Reference Laboratory, National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and PreventionNational Tuberculosis Reference Laboratory, National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and PreventionAbstract Background Pyrazinamide still may be a useful drug for treatment of rifampin-resistant (RR-TB) or multidrug-resistant tuberculosis (MDR-TB) in China while awaiting scale up of new drugs and regimens including bedaquiline and linezolid. The level of pyrazinamide resistance among MDR-TB patients in China is not well established. Therefore, we assessed pyrazinamide resistance in a representative sample and explored determinants and patterns of pncA mutations. Methods MDR-TB isolates from the 2007 national drug resistance survey of China were sub-cultured and examined for pyrazinamide susceptibility by BACTEC MGIT 960 method. pncA mutations were identified by sequencing. Characteristics associated with pyrazinamide resistance were analyzed using univariable and multivariable log-binominal regression. Results Of 401 MDR-TB isolates, 324 were successfully sub-cultured and underwent drug susceptibility testing. Pyrazinamide resistance was prevalent in 40.7% of samples, similarly among new and previously treated MDR-TB patients. Pyrazinamide resistance in MDR-TB patients was associated with lower age (adjusted OR 0.54; 95% CI, 0.34–0.87 for those aged ≧60 years compared to < 40 years). Pyrazinamide resistance was not associated with gender, residential area, previous treatment history and Beijing genotype. Of 132 patients with pyrazinamide resistant MDR-TB, 97 (73.5%) had a mutation in the pncA gene; with 61 different point mutations causing amino acid change, and 11 frameshifts in the pncA gene. The mutations were scattered throughout the whole pncA gene and no hot spot region was identified. Conclusions Pyrazinamide resistance among MDR-TB patients in China is common, although less so in elderly patients. Therefore, pyrazinamide should only be used for treatment of RR/MDR-TB in China if susceptibility is confirmed. Molecular testing for detection of pyrazinamide resistance only based on pncA mutations has certain value for the rapid detection of pyrazinamide resistance in MDR-TB strains but other gene mutations conferring to pyrazinamide resistance still need to be explored to increase its predictive ability .https://doi.org/10.1186/s12879-020-4758-9Multidrug-resistant tuberculosisPyrazinamideResistancepncA |
| spellingShingle | Hui Xia Susan van den Hof Frank Cobelens Yang Zhou Bing Zhao Shengfen Wang Yanlin Zhao Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China BMC Infectious Diseases Multidrug-resistant tuberculosis Pyrazinamide Resistance pncA |
| title | Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China |
| title_full | Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China |
| title_fullStr | Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China |
| title_full_unstemmed | Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China |
| title_short | Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China |
| title_sort | value of pyrazinamide for composition of new treatment regimens for multidrug resistant mycobacterium tuberculosis in china |
| topic | Multidrug-resistant tuberculosis Pyrazinamide Resistance pncA |
| url | https://doi.org/10.1186/s12879-020-4758-9 |
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