Molecular Determinants of Ethionamide Resistance in Clinical Isolates of <i>Mycobacterium tuberculosis</i>

Background: Ethionamide and prothionamide are now included in group C of the WHO recommended drugs for the treatment of tuberculosis resistant to rifampicin and multidrug-resistant tuberculosis. The clinical relevance of ethionamide and prothionamide has increased with the wide spread of resistant t...

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Main Authors: Anastasia Ushtanit, Elena Kulagina, Yulia Mikhailova, Marina Makarova, Svetlana Safonova, Danila Zimenkov
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/11/2/133
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Summary:Background: Ethionamide and prothionamide are now included in group C of the WHO recommended drugs for the treatment of tuberculosis resistant to rifampicin and multidrug-resistant tuberculosis. The clinical relevance of ethionamide and prothionamide has increased with the wide spread of resistant tuberculosis. Methods: We retrospectively analyzed 349 clinical isolates obtained between 2016 and 2020. The susceptibility to ethionamide was tested using both the Bactec<sup>TM</sup> MGIT<sup>TM</sup> 960 system and the Sensititre<sup>TM</sup> MYCOTB plate. Results: The MIC of ethionamide increases with the total resistance of the isolates in a row from susceptible to XDR strains. A significant part of the isolates have a MIC below the breakpoint: 25%, 36%, and 50% for XDR, pre-XDR, and MDR strains. Sensitivity and specificity of detection of mutations were 96% and 86% using MGIT resistance as a reference. Conclusions: Phenotypic methods for testing ethionamide are imperfectly correlated, and the isolates with MIC of 5 mg/L have the intermediate resistance. A significant proportion of resistant TB cases are susceptible and eligible for ethionamide treatment. Resistance could be explained using only analysis of loci <i>ethA</i>, P<i><sub>fabG1</sub></i>, and <i>inhA</i> for most isolates in the Moscow region. The promoter mutation P<i><sub>fabG1</sub></i> c(-15)t predicts resistance to ethionamide with high specificity but low sensitivity.
ISSN:2079-6382