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Background <p>Although many studies have examined the connection between mutations in the <i>rpoB</i> gene and drug resistance, the impact of common mutations on treatment outcomes for RR-TB is not yet fully understood.</p> Objectives <p>This study explores the relationship between <i>rpoB</i> gene mutations and drug-resistant phenotypes, assesses their role in predicting RR-TB prognosis, and investigates the impact of disputed <i>rpoB</i> mutations in <i>M. tuberculosis</i> on treatment outcomes.</p> Methods <p>192 rifampicin-resistant isolates were retested for drug susceptibility and gene sequencing. Minimum inhibitory concentrations (MICs) were determined for 98 isolates with disputed <i>rpoB</i> gene mutations. These mutations can cause low-level resistance to rifampicin, leading to inconsistencies in drug susceptibility testing and impacting medication therapy decisions.</p> Results <p>Of 192 cases, 116 (60.4%) achieved successful outcomes, while 76 (39.6%) were unsuccessful. Among the 98 isolates tested for phenotypic drug susceptibility testing (DST) based on minimum inhibitory concentration (MIC), 67 (68.4%) showed high-level resistance with a MIC of ≥ 1&#xa0;µg/mL. In contrast, 31 (31.6%) drug-susceptible tuberculosis isolates exhibited low-level resistance with a MIC of &lt; 1.0&#xa0;µg/mL. Of the 31 isolates with low-level resistance, 14 (45.2%) had successful treatment outcomes, while 17 (54.8%) did not. Among the 67 isolates with high-level resistance, 41 (61.2%) achieved successful outcomes, whereas 26 (38.8%) did not. In analysing the 14 codons of the Rifampicin Resistance Determining Region (RRDR) of the <i>rpoB</i> gene, the Leu430Pro codon showed the highest odds ratio (OR) of 2.98 (95% CI: 0.96–9.27) with a <i>p</i>-value of 0.0591, indicating statistically not significant. However, this suggests a potential association with rifampicin resistance that requires further investigation, particularly in areas with high drug-resistant tuberculosis prevalence. Other reported variants had lower odds ratios: Asp435Val with 1.23 (95% CI: 0.32–4.75), Asp435Tyr with 1.86 (95% CI: 0.60–5.76), His445Tyr with 1.16 (95% CI: 0.47–2.91), and Ser450Leu with 1.44 (95% CI: 0.81–2.58).</p> Conclusions <p>This study indicates that low-level rifampicin mono-resistance in tuberculosis (TB) patients is associated with poor clinical outcomes. A mutation at the Leu430Pro codon showed the highest odds ratio of 2.98 (<i>p</i>-value 0.0591), suggesting a potential association with rifampicin resistance that warrants further research, especially in areas with high drug-resistant TB. It highlights the need for more aggressive treatment strategies for patients with low-level rifampicin resistance, even if they seem solely mono-resistant.</p>

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Impact of rpoB gene mutations and Rifampicin-resistance levels on treatment outcomes in Rifampicin-resistant tuberculosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月27日

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  • Maria Jose Vadakunnel,
  • Vijayalakshmi Jawaharlal Nehru,
  • Usharani Brammacharry,
  • Venkateswari Ramachandra,
  • Suganthi Palavesam,
  • Anbazhagi Muthukumar,
  • Balasundaram Revathi Mani,
  • Sriramkumar S. R,
  • Gunavathy Pradhabane,
  • Azger Dusthackeer VN,
  • Sangeetha Subramani,
  • Muthuraj Muthaiah,
  • Govindarajan Soundappan

摘要

Background

Although many studies have examined the connection between mutations in the rpoB gene and drug resistance, the impact of common mutations on treatment outcomes for RR-TB is not yet fully understood.

Objectives

This study explores the relationship between rpoB gene mutations and drug-resistant phenotypes, assesses their role in predicting RR-TB prognosis, and investigates the impact of disputed rpoB mutations in M. tuberculosis on treatment outcomes.

Methods

192 rifampicin-resistant isolates were retested for drug susceptibility and gene sequencing. Minimum inhibitory concentrations (MICs) were determined for 98 isolates with disputed rpoB gene mutations. These mutations can cause low-level resistance to rifampicin, leading to inconsistencies in drug susceptibility testing and impacting medication therapy decisions.

Results

Of 192 cases, 116 (60.4%) achieved successful outcomes, while 76 (39.6%) were unsuccessful. Among the 98 isolates tested for phenotypic drug susceptibility testing (DST) based on minimum inhibitory concentration (MIC), 67 (68.4%) showed high-level resistance with a MIC of ≥ 1 µg/mL. In contrast, 31 (31.6%) drug-susceptible tuberculosis isolates exhibited low-level resistance with a MIC of < 1.0 µg/mL. Of the 31 isolates with low-level resistance, 14 (45.2%) had successful treatment outcomes, while 17 (54.8%) did not. Among the 67 isolates with high-level resistance, 41 (61.2%) achieved successful outcomes, whereas 26 (38.8%) did not. In analysing the 14 codons of the Rifampicin Resistance Determining Region (RRDR) of the rpoB gene, the Leu430Pro codon showed the highest odds ratio (OR) of 2.98 (95% CI: 0.96–9.27) with a p-value of 0.0591, indicating statistically not significant. However, this suggests a potential association with rifampicin resistance that requires further investigation, particularly in areas with high drug-resistant tuberculosis prevalence. Other reported variants had lower odds ratios: Asp435Val with 1.23 (95% CI: 0.32–4.75), Asp435Tyr with 1.86 (95% CI: 0.60–5.76), His445Tyr with 1.16 (95% CI: 0.47–2.91), and Ser450Leu with 1.44 (95% CI: 0.81–2.58).

Conclusions

This study indicates that low-level rifampicin mono-resistance in tuberculosis (TB) patients is associated with poor clinical outcomes. A mutation at the Leu430Pro codon showed the highest odds ratio of 2.98 (p-value 0.0591), suggesting a potential association with rifampicin resistance that warrants further research, especially in areas with high drug-resistant TB. It highlights the need for more aggressive treatment strategies for patients with low-level rifampicin resistance, even if they seem solely mono-resistant.