Characterization of Genetic Variants Associated with Rifampicin Resistance Level in Mycobacterium tuberculosis Clinical Isolates Collected in Guangzhou Chest Hospital, China

Hameed, H. M. Adnan; Fang, Cuiting; Li, Yong; Ju, Yanan; Han, Xingli; Gao, Yurui; Wang, Shuai; Chiwala, Gift; Tan, Yi; Guan, Ping; Hu, Jinxing; Xiong, Xiaozhen; Peng, Jiacong; Yang, Lin; Hussain, Muzammal; Zhong, Nanshan; Маслов, Д. А.; Cook, Gregory M.; Liu, Jianxiong; Zhang, Tianyu

doi:10.2147/idr.s375869

Cited by 8 publications

(8 citation statements)

References 45 publications

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“…However, it could be influenced by different regions and genetic strains. In a study that occurred in Guangzhou Chest Hospital of China, 85.71% were RIF-resistant, of which 38% were MDR-TB [35]. A study from Myanmar showed 62% isolates had RIF resistance [36].…”

Section: Discussionmentioning

confidence: 99%

Drug Resistance and Molecular Characteristics of Mycobacterium tuberculosis: A Single Center Experience

Chen

Feng

et al. 2022

JPM

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In recent years, the incidence of tuberculosis (TB) and mortality caused by the disease have been decreasing. However, the number of drug-resistant tuberculosis patients is increasing rapidly year by year. Here, a total of 380 Mycobacterium tuberculosis (MTB)-positive formalin-fixed and paraffin-embedded tissue (FFPE) specimens diagnosed in the Department of Pathology of the Eighth Medical Center, Chinese PLA General Hospital were collected. Among 380 cases of MTB, 85 (22.37%) were susceptible to four anti-TB drugs and the remaining 295 (77.63%) were resistant to one or more drugs. The rate of MDR-TB was higher in previously treated cases (52.53%) than in new cases [(36.65%), p < 0.05]. Of previously treated cases, the rate of drug resistance was higher in females than in males (p < 0.05). Among specimens obtained from males, the rate of drug resistance was higher in new cases than in previously treated cases (p < 0.05). Of mutation in drug resistance-related genes, the majority (53/380, 13.95%) of rpoB gene carried the D516V mutation, and 13.42% (51/380) featured mutations in both the katG and inhA genes. Among the total specimens, 18.68% (71/380) carried the 88 M mutation in the rpsL gene, and the embB gene focused on the 306 M2 mutation with a mutation rate of 19.74%. Among the resistant INH, the mutation rate of −15 M was higher in resistance to more than one drug than in monodrug-resistant (p < 0.05). In conclusion, the drug resistance of MTB is still very severe and the timely detection of drug resistance is conducive to the precise treatment of TB.

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Section: Discussionmentioning

confidence: 99%

Drug Resistance and Molecular Characteristics of Mycobacterium tuberculosis: A Single Center Experience

Chen

Feng

et al. 2022

JPM

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“…The emergence of MDR-TB is a serious public health problem. 34 The SLDs have to be used for treatment of MDR/XDR-TB patients but are consistently difficult with less effectiveness, less availability in low-income countries, more toxicity, and higher costs. Susceptibility testing using MIC instead of the CCs shows that some FLDs act inhibitory in slightly higher concentrations in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…The type and frequency of rpoB mutations related to RIF resistance may vary depending on the setting and level of resistance. 34 When compared to M. tuberculosis populations with isolates exhibiting high MICs, isolates with low-level resistance may have lower fitness in the presence of RIF. The cost of resistance has been identified as a crucial factor in the spread of DR-TB strains.…”

Section: Discussionmentioning

confidence: 99%

“…25,[31][32][33] The MIC was determined in triplicate for anti-TB drugs against each isolate using REMA through visual reading of the color change in 96-well microplates. 25,[31][32][33][34] The individual MICs for INH, RIF, LEV and EMB were determined for each isolate and H37Rv reference strain using a serial two-fold micro-dilution of each drug's working solution concentration with the final MIC ranges of 1-0.06µg/mL for INH, 2-0.03µg/mL for RIF, 27,28 8-0.125µg/mL for LEV 15 and 16-0.25µg/mL for EMB. 29,30 A color change from blue to pink/purple was considered as bacterial growth by reducing of resazurin.…”

Section: Resazurin-based Colorimetric Microtiter Assaymentioning

confidence: 99%

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Insights into the in-vitro Susceptibility and Drug–Drug Interaction Profiles Against Drug-Resistant and Susceptible Mycobacterium tuberculosis Clinical Isolates in Amhara, Ethiopia

Seid,

Girma,

Dereb

et al. 2024

IDR

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Background In Ethiopia, tuberculosis (TB) is a major public health problem. The aim of the study was to determine the in vitro susceptibility level of drugs and drug interaction profiles against drug-resistant and susceptible M. tuberculosis clinical isolates. A laboratory-based cross-sectional study was conducted between January 2023 and August 2023. GenoType MTBDRplus v.2.0 was facilitated in genetic mutation detection. Minimum inhibitory concentration (MIC) was determined using resazurin microtitre assay (REMA), while fractional inhibitory concentration index (FICI) using resazurin drug combination microtitre assay (REDCA) for in vitro quantitative susceptibility and drug interaction prediction. Results Among 32 clinical isolates, a total of 14 (43.8%) RIF, 20 (62.5%) INH, 2 (6.3%) EMB-related resistant and 14 (43.8%) MDR isolates were identified. Five of RIF-resistant isolates (55.6%) carrying rpoB common mutations at codon S450L were associated with high levels of RIF-resistance with MICs of ≥ 2μg/mL, whereas 100% of isolates harboring rpoB substitutions at codons D435V and H445Y were linked with moderate or low-level RIF-resistance in the MIC ranges from 0.5 to 1μg/mL. A proportion of 81.8% of isolates harboring katG S315T mutations were associated with high-level INH resistance (MIC ≥ 1μg/mL), while the 18.2% of isolates with S315T katG mutations and 100% of isolates with inhA C-15T mutations were linked to the low-level of INH resistance with MIC variability from 0.25 to 0.5μg/mL. Our results indicated that most FICIs of the dual drugs INH+RIF and INH+LEV combination for 9 (28.1%) and 4 (12.5%) INH-resistant isolates, respectively, were ≤0.5, whereas triple drugs INH+RIF+EMB, INH+RIF+LEV and INH+EMB+LEV combination for 6 (18.8%), 11 (34.4%) and 8 (25%) INH-resistant isolates were from 0.62 to 0.75, all showed synergistic effect. Conclusion The study highlights that isolates with rpoB S450L and katG S315T substitutions were associated with high level of RIF and INH resistance. It is concluded that REDCA can quantitatively determine anti-mycobacterial synergy and that LEV being of potential use against INH-resistant isolates including MDR-TB when combined with RIF+INH and INH+EMB.

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“…Infected individuals can unknowingly spread the disease to others, as the progression from latent TB infection to active TB disease can occur gradually over time. Also, in most cases, the infected patients remain undiagnosed, posing a significant risk of widespread transmission of infection ( 3 ). The presence of undiagnosed rifampicin-resistant (RIF R ) cases has exacerbated the global health situation and contributed to the escalating burden of TB ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Distribution of common and rare drug resistance patterns in Mycobacterium tuberculosis clinical isolates revealed by GenoType MTBDRplus and MTBDRsl assay

Khan,

Zhu,

Guan

et al. 2023

J Thorac Dis

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Background Tuberculosis (TB) remains a significant global health emergency caused by Mycobacterium tuberculosis (Mtb). The epidemiology, transmission, genotypes, mutational patterns, and clinical consequences of TB have been extensively studied worldwide, however, there is a lack of information regarding the epidemiology and mutational patterns of Mtb in Pakistan, specifically concerning the prevalence of multi-drug resistant TB (MDR-TB). Methods This study aimed to investigate the incidence of Mtb and associated mutational patterns using the line probe assay (LPA). Previous studies have reported a high frequency of mutations in the rpoB , inhA , and katG genes, which are associated with resistance to rifampicin (RIF) and isoniazid (INH). Therefore, the current study utilized LPA to detect mutations in the rpoB , katG , and inhA genes to identify multi-drug resistant Mtb. Results LPA analysis of a large pool of Mtb isolates, including samples from 241 sputum-positive patients, revealed that 34.85% of isolates were identified as MDR-TB, consistent with reports from various regions worldwide. The most prevalent mutations observed were rpoB S531L and inhA promoter C15T, which were associated with resistance to RIF and INH, respectively. Conclusions This study highlights the effectiveness of GenoType MTBDR plus and MTBDR sl assays as valuable tools for TB management. These assays enable rapid detection of resistance to RIF, INH, and fluoroquinolones (FQs) in Mtb clinical isolates, surpassing the limitations of solid and liquid media-based methods. The findings contribute to our understanding of MDR-TB epidemiology and provide insights into the genetic profiles of Mtb in Pakistan, which are essential for effective TB control strategies.

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Characterization of Genetic Variants Associated with Rifampicin Resistance Level in Mycobacterium tuberculosis Clinical Isolates Collected in Guangzhou Chest Hospital, China

Cited by 8 publications

References 45 publications

Drug Resistance and Molecular Characteristics of Mycobacterium tuberculosis: A Single Center Experience

Drug Resistance and Molecular Characteristics of Mycobacterium tuberculosis: A Single Center Experience

Insights into the in-vitro Susceptibility and Drug–Drug Interaction Profiles Against Drug-Resistant and Susceptible Mycobacterium tuberculosis Clinical Isolates in Amhara, Ethiopia

Distribution of common and rare drug resistance patterns in Mycobacterium tuberculosis clinical isolates revealed by GenoType MTBDRplus and MTBDRsl assay

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