Dilemmas with ethionamide susceptibility testing of Mycobacterium tuberculosis: A microbiologist &amp; physician′s nightmare

Varma-Basil, Mandira; Prasad, Rajendra

doi:10.4103/0971-5916.171272

Cited by 4 publications

(4 citation statements)

References 10 publications

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“…There were 17 (53%) isolates in which n.C-15T mutation was identified but the phenotype was susceptible. This indicated the difficulty in performing the phenotypic testing for ethionamide as reported previously ( 17 ).…”

Section: Resultsmentioning

confidence: 51%

Mycobacterium tuberculosis Lineages Associated with Mutations and Drug Resistance in Isolates from India

et al. 2022

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Section: Resultsmentioning

confidence: 51%

Mycobacterium tuberculosis Lineages Associated with Mutations and Drug Resistance in Isolates from India

et al. 2022

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“…The lower sensitivity of 65.9% (95%CI: 57.1-73.6) observed for ETH compared to 97.6% relative to sequencing, was suggestive of the presence of additional mutations in targets not covered by the assay or false ETH resistance on phenotypic DST. The latter cannot be confirmed since pDST was not performed for discordant results, however ETH pDST is known to be unreliable (22). Based on these findings ETH resistance can be ruled in and not ruled out using the MTB/XDR assay, in agreement with previous observations (23).…”

Section: Discussionmentioning

confidence: 99%

Performance evaluation of the Xpert MTB/XDR test for the detection of drug resistance toMycobacterium tuberculosisamong people diagnosed with tuberculosis in South Africa

Omar,

Louw,

Ismail

et al. 2024

Preprint

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Background: Tuberculosis (TB) remains a significant public health concern in South Africa, with high incidence rates and a growing burden of drug-resistant TB. This study aimed to assess the diagnostic performance of the Xpert MTB/XDR test, a novel molecular assay, for detecting drug resistance in TB patients using archived sputum sediments. Methods: The study involved a comprehensive analysis of 322 samples collected from presumptive TB patients between 2016 - 2019 across South Africa, previously characterized by phenotypic and genotypic methods. The Xpert MTB/XDR test was evaluated for its ability to detect resistance to isoniazid (INH), ethionamide (ETH), fluoroquinolones (FLQ), and second-line injectable drugs (SLID) compared to phenotypic drug susceptibility testing (pDST) and whole-genome sequencing (WGS). The Xpert MTB/RIF Ultra and G4 tests were performed to determine agreement with this test for TB detection. Findings: The Xpert MTB/XDR test performance showed excellent sensitivity and specificity for detecting Mycobacterium tuberculosis (M. tuberculosis), with a sensitivity of 98.3% and specificity of 100% compared to culture. The sensitivities using a composite reference standard, pDST and sequencing, were over 90% for INH, FLQ, AMK, KAN, and CAP resistance, meeting the WHO target product profile criteria for this class. A lower sensitivity of 65.9% for ETH resistance was observed, driven by the limited targets covered by the assay. Interpretation: The Xpert MTB/XDR test offers a promising solution for the rapid detection of drug-resistant TB in South Africa. It could significantly enhance TB control efforts in this setting and contribute to improved patient care and management.

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“…The consistent monotherapy of ethionamide gradually facilitates its resistance in Mycobacterium tuberculosis. Ethionamide resistance of Mycobacterium tuberculosis generally attributes to the spontaneous mutations in ethR and ethA genes (Varma-Basil & Prasad, 2015) [34]. The clinicians require determining the risk of ethionamide resistance in MDR-TB patients following the prolonged administration of category-4 therapy.…”

Section: Mdr-tb Treatment Approachesmentioning

confidence: 99%

“…The unavailability of a robust ethionamide susceptibility testing intervention challenges the proactive assessment of MDR-TB prognosis and therapeutic outcomes (Varma-Basil & Prasad, 2015) [34]. The clinicians require evaluating the ethionamide resistant strains of Mycobacterium tuberculosis for minimizing the risk of category-4 treatment failure in MDR-TB patients.…”

Section: Therapeutic Challenges Of Mdr-tb Drugsmentioning

confidence: 99%

The Emerging Global Challenge of Multidrug-Resistant Tuberculosis (MDR-TB) Therapy (An Expert Opinion)

Rahman¹

2019

TIJCR

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MDR-TB (Multidrug-Resistant Tuberculosis) reportedly proves to be the greatest health care burden responsible for a substantial deterioration of health-related quality of life of underprivileged people across the globe. MDR-TB. The late diagnosis of MDR-TB, absence of standardized therapy, and treatment delays are some of the significant factors that substantially elevate comorbidity and mortality risk of the affected patients. HIV positive MDR-TB patients experience a drastic reduction in their life expectancy and wellness outcomes. The WHO guidelines recommend various treatment regimens for the systematic treatment of MDR-TB. Category-4 therapy proves to be the standard treatment option for MDR-TB patients. However, the clinicians still require closely monitoring the clinical history of their MDR-TB patients/suspects in the context of including the most appropriate drugs in category-4 therapy. The elevated side-effects of MDR-TB therapies lead to treatment non-compliance and discontinuation of category-4 intervention. This eventually increases the frequency of MDR-TB-related comorbidities and mortality on a global scale. The clinicians and researchers require revisiting the already approved MDR-TB treatment regimens in the context of modifying the drugs' combinations and/or dosages for decreasing the length of overall therapy while minimizing the risk of side effects. The researchers require undertaking prospective clinical trials to evaluate the therapeutic targets of unapproved MDR-TB treatment drugs in the context of optimizing the treatment combinations. Furthermore, the enhancement of drug susceptibility techniques and the thorough clinical examination of each MDR-TB case are highly required to effectively improve the overall quality of the selected antituberculosis therapy.

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Dilemmas with ethionamide susceptibility testing of Mycobacterium tuberculosis: A microbiologist & physician′s nightmare

Cited by 4 publications

References 10 publications

Mycobacterium tuberculosis Lineages Associated with Mutations and Drug Resistance in Isolates from India

Mycobacterium tuberculosis Lineages Associated with Mutations and Drug Resistance in Isolates from India

Performance evaluation of the Xpert MTB/XDR test for the detection of drug resistance toMycobacterium tuberculosisamong people diagnosed with tuberculosis in South Africa

The Emerging Global Challenge of Multidrug-Resistant Tuberculosis (MDR-TB) Therapy (An Expert Opinion)

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