Phenotypic and molecular characterization of pyrazinamide resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Ningbo, China

Yang Che, Dingyi Bo, Xiang Lin, Tong Chen, Tianfeng He, Yi Lin

Research output: Journal PublicationArticlepeer-review

3 Citations (Scopus)

Abstract

Background: Detection of pyrazinamide (PZA) resistance in Mycobacterium tuberculosis (TB) patients is critical, especially in dealing with multidrug-resistant Mycobacterium tuberculosis (MDR-TB) case. Up to date, PZA drug susceptibility testing (DST) has not been regularly performed in China. The prevalence and molecular characteristics of PZA resistance in M.tuberculosis isolates, especially MDR-TB have not been studied in Ningbo, China. This study aimed to analyze the phenotypic and molecular characterization of PZA resistance among MDR-TB isolates in Ningbo. Methods: A total of 110 MDR-TB isolates were collected from the TB patients who were recorded at local TB dispensaries in Ningbo. All clinical isolates were examined by drug susceptibility testing and genotyping. DNA sequencing was used to detect mutations in the pncA gene associated with PZA resistance. Results: The prevalence of PZA resistance among MDR-TB strains in Ningbo was 59.1%. With regard to the history and the outcome of treatments among MDR-TB cases, the percentages of re-treated MDR-TB patients in the PZA-resistant group and of successful patients in PZA-susceptible group were significantly higher than the ones in the PZA-susceptible group and in the PZA-resistant group, respectively (P = 0.027, P = 0.020). The results showed that the resistance of streptomycin (67.7% vs 46.7%, P = 0.027), ethambutol (56.9% vs 33.3%, P = 0.015), ofloxacin (43.1% vs 11.1%, P = 0.000), levofloxacin (43.1% vs 11.1%, P = 0.000), pre-XDR (pre-Xtensively Drug Resistance) (38.5% vs 15.6%, P = 0.009), were more frequently adverted among PZA-resistant isolates compared with PZA-susceptible isolates. In addition, 110 MDR-TB was composed of 87 (PZA resistant, 78.5%) Beijing strains and 23 (PZA resistant, 21.5%) non-Beijing strains. Fifty-four out of 65 (83.1%) PZA-resistant MDR strains harbored a mutation located in the pncA gene and the majority (90.7%) were point mutations. Compared with the phenotypic characterization, DNA sequencing of pncA has sensitivity and specificity of 83.1 and 95.6%. Conclusion: The mutations within pncA gene was the primary mechanism of PZA resistance among MDR-TB and DNA sequencing of pncA gene could provide a rapid detection evidence in PZA drug resistance of MDR-TB in Ningbo.

Original languageEnglish
Article number605
JournalBMC Infectious Diseases
Volume21
Issue number1
DOIs
Publication statusPublished - Dec 2021

Keywords

  • Multidrug-resistant
  • Mycobacterium tuberculosis
  • Resistance
  • pncA gene

ASJC Scopus subject areas

  • Infectious Diseases

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