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Objective <p><i>Multidrug-resistant tuberculosis</i> (MDR-TB) remains a major public health challenge in China. Hainan, China’s largest tropical island, possesses distinct socio-geographical features. However, the drug resistance patterns and molecular epidemiology of MDR-TB in this region have not been fully elucidated. This study aimed to assess the correlation between drug resistance genotypes and phenotypic resistance levels in <i>multidrug-resistant Mycobacterium tuberculosis</i> (MDR-MTB) strains collected from Hainan Island, using whole-genome sequencing (WGS) and phenotypic drug susceptibility testing (DST).</p> Methods <p>MDR-MTB strains isolated from patients on Hainan Island (2019–2021) were analyzed. Minimum inhibitory concentrations (MIC) for 15 anti-TB drugs were determined by broth microdilution (BMD). Whole-genome sequencing (WGS) was performed using Illumina NovaSeq 6000. Genotypic resistance was predicted via TB-Profiler, and correlations between resistance mutations and MIC levels were assessed.</p> Results <p>A total of 209 MDR-MTB strains were analyzed. Strains of lineage 2.2 exhibited significantly higher resistance to ethambutol (EMB) compared to non-lineage 2 strains (<i>P</i> &lt; 0.05). The sensitivity of WGS in predicting resistance to first-line drugs isoniazid (INH), rifampicin (RIF), EMB, and pyrazinamide (PZA) was 94.7%, 99.0%, 96.5%, and 80.8%, respectively. However, specificity for EMB and PZA was lower at 60.2% and 79.4%. WGS also demonstrated high sensitivity and specificity (&gt; 95%) for second-line injectable aminoglycosides (amikacin [AMK], capreomycin [CPM], and kanamycin [KM]), but sensitivity for other second-line drugs except for fluoroquinolone drug moxifloxacin (MOX, 94.4%) was below 80.0%. Notably, mutations in <i>katG</i>_S315T, <i>rpoB</i>_S450L, and <i>gyrA</i>_D94G were strongly associated with high-level resistance, while mutations in <i>fabG1</i>, <i>ahpC</i>, <i>embA</i> promoters, and <i>gyrA</i> at codon 90 were linked to low-level resistance.</p> Conclusions <p>This study quantitatively demonstrates the relationship between specific drug resistance genotypes and resistance levels. It is the first to characterize the regional resistance spectrum of MDR-MTB strains on Hainan Island. These findings offer a novel foundation for MIC-based dose adjustment and the optimization of treatment strategies in this region.</p> &#xa0;Trial registration <p>MR-46–23-020530. Date of registration:2023–07-03.</p>

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Surveillance and analysis of drug resistance and drug resistance levels in multidrug resistant tuberculosis on the tropical islands of China

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月1日

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  • Jieying Wang,
  • Jinhui Dong,
  • Zhuolin Chen,
  • Yuni Xu,
  • Wenhua Qiu,
  • Shaowen Chen,
  • Hua Pei,
  • Yeteng Zhong

摘要

Objective

Multidrug-resistant tuberculosis (MDR-TB) remains a major public health challenge in China. Hainan, China’s largest tropical island, possesses distinct socio-geographical features. However, the drug resistance patterns and molecular epidemiology of MDR-TB in this region have not been fully elucidated. This study aimed to assess the correlation between drug resistance genotypes and phenotypic resistance levels in multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) strains collected from Hainan Island, using whole-genome sequencing (WGS) and phenotypic drug susceptibility testing (DST).

Methods

MDR-MTB strains isolated from patients on Hainan Island (2019–2021) were analyzed. Minimum inhibitory concentrations (MIC) for 15 anti-TB drugs were determined by broth microdilution (BMD). Whole-genome sequencing (WGS) was performed using Illumina NovaSeq 6000. Genotypic resistance was predicted via TB-Profiler, and correlations between resistance mutations and MIC levels were assessed.

Results

A total of 209 MDR-MTB strains were analyzed. Strains of lineage 2.2 exhibited significantly higher resistance to ethambutol (EMB) compared to non-lineage 2 strains (P < 0.05). The sensitivity of WGS in predicting resistance to first-line drugs isoniazid (INH), rifampicin (RIF), EMB, and pyrazinamide (PZA) was 94.7%, 99.0%, 96.5%, and 80.8%, respectively. However, specificity for EMB and PZA was lower at 60.2% and 79.4%. WGS also demonstrated high sensitivity and specificity (> 95%) for second-line injectable aminoglycosides (amikacin [AMK], capreomycin [CPM], and kanamycin [KM]), but sensitivity for other second-line drugs except for fluoroquinolone drug moxifloxacin (MOX, 94.4%) was below 80.0%. Notably, mutations in katG_S315T, rpoB_S450L, and gyrA_D94G were strongly associated with high-level resistance, while mutations in fabG1, ahpC, embA promoters, and gyrA at codon 90 were linked to low-level resistance.

Conclusions

This study quantitatively demonstrates the relationship between specific drug resistance genotypes and resistance levels. It is the first to characterize the regional resistance spectrum of MDR-MTB strains on Hainan Island. These findings offer a novel foundation for MIC-based dose adjustment and the optimization of treatment strategies in this region.

 Trial registration

MR-46–23-020530. Date of registration:2023–07-03.