The nature of genotypic resistance to fluoroquinolones in Mycobacterium tuberculosis circulating in Russian Federation

About authors

Central Tuberculosis Research Institute, Moscow, Russia

Correspondence should be addressed: Sofia N. Andreevskaya
Yauzskaya Alleya, 2, str. 1А, Moscow, 107564, Russia; ur.liam@aifosdna

About paper

Funding: the study was conducted as part of the State Assignment № 122041100246-3 for the Central Tuberculosis Research Institute, “Intra- and Inter- species Polymorphism of Mycobacteria in Patients with Tuberculosis and Mycobacteriosis Who Receive Specific Therapy”.

Author contribution: Ergeshov A, Chernousova LN — study design; Larionova EE, Kiseleva EA — data acquisition; Smirnova TG — data analysis; Andreevskaya SN — manuscript writing, literature review; all authors contributed to the discussion.

Received: 2022-10-10 Accepted: 2022-10-24 Published online: 2022-10-31

Fluoroquinolones are the main group of drugs used for treatment of multidrug resistant tuberculosis (MDR-TB). The study was aimed to assess the diversity of mutation in the gyrA gene and to evaluate the association of gyrA mutations with the phenotypic resistance to levofloxacin and the general drug resistance profile of the pathogen. The study involved assessment of diagnostic materials obtained from 2836 patients with pulmonary tuberculosis. TB-BIOCHIP-2 and AmplitubeFQ-RV kits were used for identification of the gyrA mutations. Phenotypic drug susceptibility of M. tuberculosis (MTB) was defined using the BACTEC MGIT 960 test system. It was shown that mutations D94G (41.63%; 95% CI: 38.03–45.32%) and A90V (21.32%; 95% CI: 18.44–24.50%) prevailed in MBT, although some isolates carrying these mutations were obtained from the newly diagnosed patients with pulmonary tuberculosis. It was found that mutation D94A was not strongly associated with the phenotypic resistance to fluoroquinolones. Fluoroquinolone resistance was usually associated with multiple drug resistance (93.52%; 95% CI 91.43–95.12%). In 2.31% (95% CI 1.78–3.00%) of cases, genotypic heteroresistance to fluoroquinolones was detected: mixed populations included 2–4 MTB pools with various structure of the gyrA QRDR. The results obtained lead to the conclusion that resistance to fluoroquinolones that is usually associated with the existing MDR arises in the modern MTB population. MTB carrying gyrA mutations D94G and A90V seems to be the most promising in evolutionary terms.

Keywords: resistance, M. tuberculosis, mutations, fluoroquinolones, gyrA, preXDR tuberculosis