2020PROBLEMS of Infectious and Parasitic DiseasesOpen access

ISONIAZID - MONORESISTANT TUBERCULOSIS IN BULGARIA

Stanislava Yordanova, Ana Baykova, Yuliana Atanasova, Yana Todorova, Elizabeta Bachiyska

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Abstract

Background. Isoniazid is a common drug in the treatment regimens for TB infection. Monoisoniazid resistance reduces the probability of a successful treatment outcome and increases the risk of acquiring additional drug resistance. Material and methods. For the period 2015-2016 a total of 36 TB cases were confirmed in NRL TB, Sofia, as isoniazid-monoresistant Mycobacterium tuberculosis complex. Minimum inhibitory concentration testing for isoniazid was conducted with BАСТЕС MGIT 960 System in the following concentrations of the drug: 0.1 μg/ml, 0.15μg/ml, 0.2μg/ml, 0.3μg/ml, 0.4μg/ml. Molecular testing was performed with GenoType ® MTBDRplus in order to detect the most common mutations associated with resistance to isoniazid. Results. Only 25% of the tested M. tuberculosis complex isolates with phenotypic isoniazid monoresistance had the S315T1 mutation in katG; all isolates were with MIC over 0.4 μg/ml. C15T in the promoter region of inhA was detected in 22.22% of cases and only 1 of them showed MIC below 0.4 μg/ml. No mutations were detected in nearly half of the cases (n=19, 52.78%) and most of these isolates were with lower MIC values (n=12). Conclusion. The rapid testing with GenoType ® MTBDRplus can be used as a screening procedure indicating whether further examination of isoniazid MIC is relevant in resistant M. tuberculosis and whether higher doses could be considered.

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Background. Isoniazid is a common drug in the treatment regimens for TB infection. Monoisoniazid resistance reduces the probability of a successful treatment outcome and increases the risk of acquiring additional drug resistance. Material and methods. For the period 2015-2016 a total of 36 TB cases were confirmed in NRL TB, Sofia, as isoniazid-monoresistant Mycobacterium tuberculosis complex. Minimum inhibitory concentration testing for isoniazid was conducted with BАСТЕС MGIT 960 System in the following concentrations of the drug: 0.1 μg/ml, 0.15μg/ml, 0.2μg/ml, 0.3μg/ml, 0.4μg/ml. Molecular testing was performed with GenoType ® MTBDRplus in order to detect the most common mutations associated with resistance to isoniazid. Results. Only 25% of the tested M. tuberculosis complex isolates with phenotypic isoniazid monoresistance had the S315T1 mutation in katG; all isolates were with MIC over 0.4 μg/ml. C15T in the promoter region of inhA was detected in 22.22% of cases and only 1 of them showed MIC below 0.4 μg/ml. No mutations were detected in nearly half of the cases (n=19, 52.78%) and most of these isolates were with lower MIC values (n=12). Conclusion. The rapid testing with GenoType ® MTBDRplus can be used as a screening procedure indicating whether further examination of isoniazid MIC is relevant in resistant M. tuberculosis and whether higher doses could be considered.

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Available abstract

Background. Isoniazid is a common drug in the treatment regimens for TB infection. Monoisoniazid resistance reduces the probability of a successful treatment outcome and increases the risk of acquiring additional drug resistance. Material and methods. For the period 2015-2016 a total of 36 TB cases were confirmed in NRL TB, Sofia, as isoniazid-monoresistant Mycobacterium tuberculosis complex. Minimum inhibitory concentration testing for isoniazid was conducted with BАСТЕС MGIT 960 System in the following concentrations of the drug: 0.1 μg/ml, 0.15μg/ml, 0.2μg/ml, 0.3μg/ml, 0.4μg/ml. Molecular testing was performed with GenoType ® MTBDRplus in order to detect the most common mutations associated with resistance to isoniazid. Results. Only 25% of the tested M. tuberculosis complex isolates with phenotypic isoniazid monoresistance had the S315T1 mutation in katG; all isolates were with MIC over 0.4 μg/ml. C15T in the promoter region of inhA was detected in 22.22% of cases and only 1 of them showed MIC below 0.4 μg/ml. No mutations were detected in nearly half of the cases (n=19, 52.78%) and most of these isolates were with lower MIC values (n=12). Conclusion. The rapid testing with GenoType ® MTBDRplus can be used as a screening procedure indicating whether further examination of isoniazid MIC is relevant in resistant M. tuberculosis and whether higher doses could be considered.

Key concepts: Isoniazid, INHA, Tuberculosis, Mycobacterium tuberculosis, Genotype, Drug resistance, Minimum inhibitory concentration, Medicine

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