Phenotypic and genotypic characterization of pyrazinamide resistance among multidrug-resistant Mycobacterium tuberculosis clinical isolates in Hangzhou, China

Liu, Wei; Chen, Jiazhen; Shen, Yaojie; Jin, Jialin; Wu, Jing; Sun, Feng; Wu, Yingliang; Xie, Li; Zhang, Ying; Zhang, Wenhong

doi:10.1016/j.cmi.2017.12.012

Cited by 19 publications

(27 citation statements)

References 35 publications

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“…Detection of pncA gene mutations may provide pyrazinamide susceptibility information. The concordance between pncA gene mutations and pyrazinamide susceptibility varies substantially among previous studies, ranging from lower than 50% [28,29] to higher than 75% [8,[10][11][12]30]. Our finding was similar to that of most other studies.…”

Section: Discussionsupporting

confidence: 89%

“…It is to be expected that the prevalence of resistance has increased, in line with the finding of higher prevalence among the younger group of patients, who on average have been infected more recently than older patients. The higher prevalence in more recent years from several sub-national studies in China [11][12][13][14] also support this expectation. Further studies of larger samples collected during more recent years and exploring the resistance by using of whole genome sequence may provide more accurate and deeper insights into the mechanism and associated factors of pyrazinamide resistance in China.…”

Section: Discussionmentioning

confidence: 56%

“…The reported prevalence of pyrazinamide resistance in MDR-TB isolates elsewhere varied substantially by country, ranging from 36.7 to 84.6% [17][18][19][20][21]. The range of previously reported proportions of pyrazinamide resistance in selected samples from China was 43.1-62.4% [11][12][13][14].…”

Section: Discussionmentioning

confidence: 94%

“…This partly explains the paucity of data on the prevalence of pyrazinamide resistance among MDR-TB patients in China. The available data show a large variation in pyrazinamide prevalence, which may be explained through inclusion of selected cases [11][12][13][14]. In this study, we analyzed pyrazinamide resistance, risk factors for resistance, and mutations in the pncA gene, among patients identified with MDR-TB in a nationally representative sample of TB patients in China.…”

Section: Introductionmentioning

confidence: 99%

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Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China

et al. 2020

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Background: Pyrazinamide still may be a useful drug for treatment of rifampin-resistant (RR-TB) or multidrugresistant 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 logbinominal 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 .

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China

et al. 2020

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“…When the culture results were positive, the morphology was confirmed by positive acid-fast staining response. Then, the mycobacterial strains were tested via MPB64 protein assay (Hangzhou Genesis, Hangzhou, China) and identified as NTM by a negative response or MTBC by a positive response 11 . The clinical records of inpatients with corresponding NTM isolates were anonymously reviewed and informed consent was obtained from all participants.…”

Section: Methodsmentioning

confidence: 99%

Retrospective analysis of patients with non-tuberculous mycobacteria from a primary hospital in Southeast China

Sun

et al. 2020

Sci Rep

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to achieve a comprehensive understanding of the characteristics of patients with non-tuberculous mycobacteria (NTM), patients with NTM between January 2016 and June 2019 were recruited from a primary hospital. NTM were identified based on the MBP64 protein assay. The clinical records and laboratory assay results were retrospectively reviewed. A total of 204 patients with NTM were included in the final analysis. The patients with multiple isolations were more likely accompanied with chronic obstructive pulmonary disease (copD) (p = 0.029) and arthritis (p = 0.049), but showed a lower percentage of positive t-spot results (p = 0.022). In addition, patients with multiple isolations showed a higher rate of positive acid-fast staining results and their symptom duration was more likely longer than 30 days (p = 0.019). Patients with a positive response in T-spot assay showed a higher proportion of nodular manifestation on computed tomography (ct) than those with a negative response. compared with male patients with ntM, female patients showed lower rates of positive acid-fast staining results (p = 0.03), but were more likely accompanied with COPD (p < 0.0001). The positive acid-fast staining results were closely associated with pulmonary cavities and tuberculosis antibody. patients with different NTM isolation frequencies were closely associated with coexisting diseases and examination results.

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Mutations Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis: A Review and Update

Rajendran

Palaniyandi

2022

Curr Microbiol

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Phenotypic and genotypic characterization of pyrazinamide resistance among multidrug-resistant Mycobacterium tuberculosis clinical isolates in Hangzhou, China

Abstract: PZA resistance was largely associated with mutations in pncA. Mutations in rpsA and panD were also associated with PZA resistance in MDR isolates expressing wild-type pncA. The detection of mutations in pncA, rpsA and panD can be useful for the determination of PZA resistance.

Cited by 19 publications

References 35 publications

Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China

Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China

Retrospective analysis of patients with non-tuberculous mycobacteria from a primary hospital in Southeast China

Mutations Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis: A Review and Update

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