Molecular Determinants of Ethionamide Resistance in Clinical Isolates of Mycobacterium tuberculosis .

Autor: Ushtanit A; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Kulagina E; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Mikhailova Y; The Moscow Research and Clinical Center for Tuberculosis Control, Moscow Government Health Department, 107014 Moscow, Russia., Makarova M; The Moscow Research and Clinical Center for Tuberculosis Control, Moscow Government Health Department, 107014 Moscow, Russia., Safonova S; The Moscow Research and Clinical Center for Tuberculosis Control, Moscow Government Health Department, 107014 Moscow, Russia., Zimenkov D; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Jazyk: angličtina
Zdroj: Antibiotics (Basel, Switzerland) [Antibiotics (Basel)] 2022 Jan 20; Vol. 11 (2). Date of Electronic Publication: 2022 Jan 20.
DOI: 10.3390/antibiotics11020133
Abstrakt: 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 TM MGIT TM 960 system and the Sensititre TM 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 ethA , P fabG1 , and inhA for most isolates in the Moscow region. The promoter mutation P fabG1 c(-15)t predicts resistance to ethionamide with high specificity but low sensitivity.
Databáze: MEDLINE
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