Isoniazid-resistant Mycobacterium tuberculosis: prevalence, resistance spectrum and genetic determinants of resistance

About authors

Laboratory of Biotechnology, Central Tuberculosis Research Institute, Moscow, Russia

Correspondence should be addressed: Sofia N. Andreevskaya
Yauzskaya alley, 2, Moscow, 107564; ur.liam@aifosdna

About paper

Funding: this study was supported by the Ministry of Science and Higher Education of the Russian Federation and carried out under the Federal Targeted Program for Research and Development in Priority Areas of Development of the Russian Scientific and Technological Complex for 2014-2020, Project № 05.586.21.0065 (Project ID RFMEFI58619X0065).

Author contribution: Ergeshov A, Chernousova LN — study design; Larionova EE, Andrievskaya IYu — data acquisition; Smirnova TG — data analysis; Andreevskaya SN — manuscript preparation, literature analysis. All authors have equally contributed to the discussion of the obtained results.

Received: 2019-12-11 Accepted: 2020-01-07 Published online: 2020-01-12

The lack of simple, rapid diagnostic tests for isoniazid-resistant rifampicin-susceptible tuberculosis infection (Hr-TB) can result in low treatment efficacy and further amplification of drug resistance. Based on the clinical data, this study sought to estimate the prevalence of Hr-TB in the general population and characterize the phenotypic susceptibility and genetic determinants of isoniazid resistance in M. tuberculosis strains. Molecular-genetic and culture-based drug susceptibility tests were performed on M. tuberculosis isolates and M. tuberculosis DNA obtained from the patients with pulmonary TB undergoing treatment at the Central Tuberculosis Research Institute between 2011 and 2018. The tests revealed that Hr-TB accounted for 12% of all TB cases in the studied sample. Hr-TB strains were either resistant to isoniazid only (45%) or had multiple resistance to 2–6 anti-TB agents. Resistance to isoniazid was caused by mutations in the katG gene. Based on the literature analysis and our own observations, we emphasize the importance of developing simple molecular drug susceptibility tests capable of detecting simultaneous resistance to rifampicin and isoniazid and the necessity of their translation into clinical practice.

Keywords: single nucleotide polymorphism, tuberculosis, Mycobacterium tuberculosis, isoniazid resistance, drug susceptibility, molecular diagnostics