In the study we obtained and analyzed the results of the development of resistance of Mycobacterium tuberculosis to the novel antitubercular drug bedaquiline. We investigate 16 strains isolated from 16 patients with pulmonary TB after bedaquiline therapy. With the help of wholegenome sequencing we detected 20 mutations in the mmpR gene and 6 mutations in the target gene atpE associated with bedaquiline resistance in vitro. It was found, that MIC values of bedaquiline were significantly higher for strains with mutations in the atpE gene than for MTB strains with mutations in the mmpR gene.

In order to study the in vitro adaptation of M.tuberculosis strains of various phylogenetic lineages and drug resistance under multistress conditions created by a lack of nutrients, reactive forms of nitrogen and oxygen, 17 strains of M.tuberculosis were studied (10 strains of the East Asian lineage of the Beijing sublineage and 7 strains Euro-American lineage). We studied the culture yield, the state of M.tuberculosis cells in culture and the secretome when cultivating strains under conditions of multistress, nitrosative stress and in optimal conditions. It has been established that M. tuberculosis strains of frequently SITs with a sensitive genotype or with widespread mutations, in contrast to strains with rare mutations and with an expanded spectrum of phenotypic drug resistance, adapt well to stress conditions in vitro. M.tuberculosis strains of the Beijing sublineage adapt to stress at an earlier time than M.tuberculosis of the Euro-American lineage; this was especially evident in the multistress model.

The aim of the work is to investigate the expression level of the main genes of multidrug resistance proteins of macroorganism somatic cells (MDR-SCM) – ABCB1, ABCC1, ABCG2 – in pulmonary tuberculomas with different inflammatory activity.
Materials and methods. Surgical material of pulmonary tuberculoma was obtained from 30 patients (16 men and 14 women). According to the results of histological examination and morphological analysis tuberculoma samples were divided into two groups: with moderate or severe inflammatory process. The level of expression of the ABCB1, ABCC1, and ABCG2 genes was evaluated for all samples by real-time polymerase chain reaction.
Results. The genes ABCB1, ABCC1, ABCG2 are expressed in the perifocal zone of tuberculomas and their expression level depends on the activity of inflammation. The highest expression level was found for the ABCB1 gene encoding the P-gp transporter protein.

This study is aimed to enhance the immune response to anti-TB drugs (anti-TBD) in vitro of circulating blood lymphocytes from patients with adverse reactions.
Methods. The immune response of lymphocytes to first-line anti-TBD was studied in 7 patients with hepatotoxic reactions (test group) and 13 patients without reactions (control group). The modified blast transformation test was used in a culture of lymphocytes in vitro; proliferative activity was increased using recombinant IL-2.
Results. The addition of IL-2 to control cultures with no anti-TBD had almost no effect on the blastogenic response of lymphocytes while the response to anti-TBD was increased 1,5–2 times. However, the stimulation index never exceeded 2. The addition of IL-2 to lymphocyte cultures of patients with hepatotoxic reactions caused an increase in the content of blasts to 4.5–5%. Different patients showed immune response simultaneously to 1 or more anti-TBD. In 3 cases the lymphocytes reacted to 3 drug combinations: R+Z+E, H+R+E and R+Z+H.
Conclusion. The modified blast transformation test is useful to identify the immune response of lymphocytes to anti-TBD in patients with hepatotoxic reactions.

The activity of bedaquiline (Bdq), a drug that is effectively used for the treatment of tuberculosis, including those with multiple (MDR) and extensively drug resistant (XDR) pathogen, was studied against rapidly growing non-tuberculous mycobacteria (NTM) belonging to Mycobacterium fortuitum complex (MFC).
Methods. А total 154 strains of MFC (78 of M. fortuitum and 76 of M. peregrinum) were examined. In addition, the drug susceptibility (DS) of these strains to 15 antibacterial drugs (ABD) was studied using the Sensitititre RapMyco test system.
Results. Тhe Bdq MIC range for M. fortuitum was found to be 0.0015–1.0 μg/mL, M. peregrinum – 0.0015–2.0 μg/mL. The MIC₅₀ for M. fortuitum was 0.015 µg/mL, MIC₉₀ was 0.25 µg/mL, and ECOFF was 0.5 µg/mL. For M. peregrinum, the corresponding values were 0.007, 0.06 and 2.0 µg/mL. As a result, only 1 (1.3%) resistant strain of M. fortuitum was detected, no resistant strains of M. peregrinum were found. When the DS of these NTM species to other ABDs were studied, it was found that M. fortuitum and M. peregrinum were highly resistant to most of them.
Conclusion. Bdq was found to be active against MFC in vitro and is likely to be effective in the chemotherapy of mycobacteriosis caused by these NTM species.

We determined the sensitivity levels to voriconazole of clinical strains of yeasts of the genera Candida (14 species), Cryptococcus (3 species), Geotrichum (one species), Hanseniaspora (one species), Saccharomyces (one species), Saprochaete (one species), Rhodotorula (2 species), Trichosporon (one species) and of filamentous fungi of the genera Acremonium (one species), Alternaria (one species), Aspergillus (12 species), Aureobasidium (one species), Cladosporium (one species), Curvularia (one species), Fusarium (2 species), Paecilomyces (2 species), Penicillium (2 species), Rhizopus (one species), Trichoderma (2 species). Voriconazole activity was high against causative agent of candidiasis, cryptococcosis, aspergillosis, phaeohyphomycosis, rare yeast mycoses (most species), hyalohyphomycosis (most species) and was low against causative agent of rhodotorulosis (Rhodotorula spp.) and zygomycosis (Rhizopus arrhizus).

The influence of latent tuberculosis infection (LTBI) on the state of the autonomic nervous system (ANS) and the level of somatotropic hormone (STH) in adolescents (100 people) aged 11 to 13 years was studied. In patients with LTBI, there was an autonomic imbalance with a predominance of sympathicotonia, which was accompanied by hyperergic reactions to the recombinant tuberculosis allergen, while in vagotonic and eutonic patients the number of hyperergic reactions was significantly less. Insignificant dynamics of the immunological test, low levels of growth hormone, and low activity of phagocytosis in adolescents with vagotonia were established, which may indicate a lack of cellular immune response. A more pronounced inversion of the immunological test with the recombinant tuberculosis allergen was revealed against the background of preventive treatment in eutonics and sympathicotonics, who had a higher level of growth hormone and phagocytosis activity initially. The established relationship between the functional state of the ANS and the growth hormone indicator, which influence the activity of phagocytosis in patients with latent tuberculosis infection, can be used to predict the effectiveness of anti-tuberculosis preventive therapy and can serve as an additional prognostic criterion for assessing the risks of developing active tuberculosis.

The literature review briefly describes the main aspects of latent tuberculosis infection and the place of tuberculosis infection among various variants of the course of tuberculosis. Latent tuberculosis infection is one of the main problems of phthisiology. Today we have made significant progress in understanding the essence of this important «component» of tuberculosis, and, therefore, the time is not far when the diagnosis, prognosis and treatment of LTBI will become quite accessible in widespread practice.

An observation of the management of active and latent tuberculosis with multidrug resistance of the causative agent of the disease in children from the same family has been presented. The efficacy and safety of a short, fully oral chemotherapy regimen with the use of new and repurposed drugs in a child with active pulmonary tuberculosis has been demonstrated. During the preventive treatment of latent tuberculosis infection for six months no adverse reactions after taking levofloxacin were reported. In one case, preventive treatment of latent MDR-TB was not carried out due to co-pathology newly diagnosed before taking the drug.