Correlation between GenoType MTBDR<i>plus</i> Assay and Phenotypic Susceptibility Test for Prothionamide in Patients with Genotypic Isoniazid Resistance

Lee, Joo Hee; Jo, Kyung‐Wook; Shim, Tae Sun

doi:10.4046/trd.2018.0027

Cited by 3 publications

(5 citation statements)

References 27 publications

(38 reference statements)

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“…The fluorescence signal intensity was collected on the LightCycler 480 System (Indianapolis Roche Group) in the FAM and TET channels, and the melting temperature TM value was obtained by identifying the peak of the melting. 7 , 12 The detection sites of INH resistance included inhA 94, inhA promoter region −17 ~ −8 mutation, and katG 315 codon mutation. The katG and inhA mutation results were recorded.…”

Section: Methodsmentioning

confidence: 99%

“…6 Based on the correlation between ETH/PTH resistance and inhA , clinicians may refer to inhA gene detection to guide the use of ETH/PTH. 3 , 4 , 7 …”

Section: Introductionmentioning

confidence: 99%

“…6 Based on the correlation between ETH/PTH resistance and inhA, clinicians may refer to inhA gene detection to guide the use of ETH/ PTH. 3,4,7 A variety of reports suggest that mutations in the inhA gene in TB strains can predict ETH/PTH resistance, although some studies have also shown that clinical strains with inhA mutations are sensitive to ETH. 3,4,7 MeltPro TB assay utilizes the real-time polymerase chain reaction (PCR) probe-based melting curve analysis technique 8 to detect the common drug-resistant mutation sites of katG, inhA and rpoB genes in MTB and rapidly diagnose INH and RIF resistance.…”

Section: Introductionmentioning

confidence: 99%

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The Value of the inhA Mutation Detection in Predicting Ethionamide Resistance Using Melting Curve Technology

Song

Wang

et al. 2021

IDR

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Objective This study aims to analyze the correlation between gene inhA mutations by melting curve technology and phenotypic drug susceptibility (DST) results of ethionamide (ETH), and evaluate whether gene inhA mutations detection can serve as a molecular marker in predicting ETH resistance. Methods A retrospective analysis was conducted on 382 strains of Mycobacterium tuberculosis (MTB) with the anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF), ETH, and others. Phenotypic drug susceptibility and the results of inhA and katG genotypes (mutation and no mutation) were obtained using the melting curve technology MeltPro TB assay. Results Of the 382 clinical strains of MTB tested, 118 (30.9%) were resistant to INH, and 28 (7.3%) were resistant to ETH. Among the 28 phenotypically ETH-resistant strains, inhA mutations accounted for 42.9% (12/28). These ETH-resistant strains comprise 35.3% (12/34) of the 34 inhA mutant strains. Of 8 single inhA mutation strains (without katG or rpoB mutation), 4(50%) were resistant to INH; however, all of these 8 strains were sensitive to ETH. Conclusion The inhA mutation test may not be a reliable predictor of ETH resistance. Mutant inhA strains are not necessarily resistant to ETH. The strains with single inhA mutation (without katG or rpoB mutation) may be effective for ETH treatment. The use of ETH in clinical medicine should be guided by gene (other than inhA alone) detection and phenotypic drug susceptibility testing.

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Section: Methodsmentioning

confidence: 99%

“…6 Based on the correlation between ETH/PTH resistance and inhA , clinicians may refer to inhA gene detection to guide the use of ETH/PTH. 3 , 4 , 7 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Value of the inhA Mutation Detection in Predicting Ethionamide Resistance Using Melting Curve Technology

Song

Wang

et al. 2021

IDR

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“…One main reason for this lower sensitivity is that these LPAs target only katG and inhA, while there are other genes associated with INH resistance, such as ahpC, furA, iniA, kasA, iniB, and iniC, exist. 17 Therefore, early assumption on how one is resistant to INH based only on the molecular DST can lead to misdiagnosis and an inappropriate choice of treatment regimen.…”

Section: Discussionmentioning

confidence: 99%

Delphi Survey on the Current and Future Korean Guidelines for Isoniazid-Monoresistant Tuberculosis

Seo¹,

Kim²,

Lee³

et al. 2023

IDR

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Purpose Isoniazid-monoresistant tuberculosis (Hr-TB) has emerged as a global challenge, necessitating detailed guidelines for its diagnosis and treatment. We aim to consolidate the Korean guidelines for Hr-TB management by gathering expert opinions and reaching a consensus. Patients and Methods A conventional Delphi method involving two rounds of surveys was conducted with 96 experts selected based on their clinical and research experience and involvement in nationwide tuberculosis studies and development of the Korean guidelines on tuberculosis. The survey consisted of three sections of questionnaires on diagnosis, treatment, and general opinions on Hr-TB. Results Among the 96 experts, 72 (75%) participated in the two rounds of the survey. A majority of experts (96%) strongly agreed on the necessity of molecular drug susceptibility testing (DST) for isoniazid and rifampin resistance in all tuberculosis patients and emphasized the importance of interpreting mutation types (inhA or katG) and additional molecular DST for fluoroquinolones for confirmed isoniazid-resistant cases. Over 95.8% of experts recommended treating Hr-TB with a combination of rifampin, ethambutol, pyrazinamide, and levofloxacin for six months, without exceeding 12 months unless necessary. They also acknowledged the drawbacks of long-term pyrazinamide use due to its side effects and agreed on shortening its duration by extending the duration of the rest of the treatment with a modified combination of choice. Conclusion This Delphi survey enabled Korean tuberculosis experts to reach a consensus on diagnosing and treating Hr-TB. These findings will be valuable for developing the upcoming revised Korean guidelines for Hr-TB management.

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“…INH resistance is classified into high- and low-level. Low-level resistance is mainly associated with mutations of inhA promoter genes [ 15 ]. We could not identify mutations of the katG gene and inhA promoter gene for all the enrolled participants, because molecular DST was not routinely performed in Korea during the study period.…”

Section: Discussionmentioning

confidence: 99%

Comparison of different regimens with or without fluoroquinolone in isoniazid-resistant tuberculosis: A multicenter cohort study

et al. 2022

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In 2018, the World Health Organization recommended a 6-month four-drug regimen (rifampicin, ethambutol, pyrazinamide, and levofloxacin) for the treatment of isoniazid-monoresistant tuberculosis. However, the regimen had very low certainty. This cohort study assessed the impact of fluoroquinolone use and initial baseline regimen on treatment effectiveness in isoniazid-monoresistant tuberculosis. This multicenter retrospective cohort study included 318 patients with isoniazid-monoresistant tuberculosis notified between 2011 and 2018 in Korea. Baseline regimens were classified into two groups, namely 6–9-month rifampicin, ethambutol, and pyrazinamide (6-9REZ) and a combination regimen of 2-month rifampicin, ethambutol, pyrazinamide and 7–10-month rifampicin and ethambutol (2REZ/7-10RE). Multivariable logistic regression was performed to assess factors associated with positive treatment outcomes. Of 318 enrolled patients, 234 (73.6%) were treated with the 6-9REZ and 103 (32.4%) with additional fluoroquinolone. In a multivariable logistic regression model comparing the 6-9REZ and 2REZ/7-10RE groups, there was no difference in the odds of positive outcomes (adjusted odds ratio = 1.08, 95% confidence interval = 0.65–1.82). Addition use of fluoroquinolone was not associated with positive treatment outcomes in the whole cohort (adjusted odds ratio = 1.41, 95% confidence interval = 0.87–2.27); however, its additional use was beneficial in the 2REZ/7-10RE subgroup (adjusted odds ratio = 3.58, 95% confidence interval = 1.32–9.75). Both initial baseline regimens, 6-9REZ and 2REZ/7-10RE, were similarly effective. Shortening of the pyrazinamide administration duration with additional fluoroquinolone use could be a safe alternative for patients with potential hepatotoxicity related to pyrazinamide.

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Correlation between GenoType MTBDRplus Assay and Phenotypic Susceptibility Test for Prothionamide in Patients with Genotypic Isoniazid Resistance

Cited by 3 publications

References 27 publications

The Value of the inhA Mutation Detection in Predicting Ethionamide Resistance Using Melting Curve Technology

The Value of the inhA Mutation Detection in Predicting Ethionamide Resistance Using Melting Curve Technology

Delphi Survey on the Current and Future Korean Guidelines for Isoniazid-Monoresistant Tuberculosis

Comparison of different regimens with or without fluoroquinolone in isoniazid-resistant tuberculosis: A multicenter cohort study

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