С целью совершенствования медицинской помощи населению г. Москвы при заболевании микобактериозами (МБ) проведены ретро- и проспективное исследования 165 больных в 2004–2018 гг. Для систематизации этиотропной терапии проведено детальное исследование лекарственной чувствительности (ЛЧ) нетуберкулезных микобактерий (НТМБ), и обнаружена широкая вариабельность спектров лекарственной устойчивости (ЛУ). Методом кластерного анализа предположили схему химиотерапии (ХТ) пациентов. Отметили важную роль хирургического лечения в комплексной терапии больных МБ. Отмечена зависимость эффективности лечения от некоторых клинических параметров, а хронический характер микобактериального воспаления определил длительное, иногда пожизненное наблюдение больных.

There has been a sharp increase in the number of diseases associated with potentially pathogenic microorganisms of the genus Mycobacterium, which differ from Mycobacterium tuberculosis. These bacteria are known as atypical mycobacteria or nontuberculosis mycobacteria (NTM), and the diseases they cause are called mycobacteriosis. NTMs include more than 20 species of acid-resistant microorganisms that are widespread in the environment and that are not members of the M. tuberculosis complex. However, the role of certain types of NTMs in the pathogenesis of human diseases is rather ambiguous. The aim of the paper was to analyse the current rise in the incidence of NTM diseases, as well as the main areas of research on early diagnosis of mycobacteriosis and the detection and testing of drug susceptibility of these microorganisms. The paper summarises current views on NTM species differences, their prevalence and pathogenicity for humans and animals. The authors analysed the main efforts aimed at diagnosis and treatment of NTM diseases. The paper cites the results of the study of NTM susceptibility/resistance to anti-tuberculosis drugs. The diagnosis of mycobacteriosis remains extremely difficult, mainly because of the similarity of the clinico-radiological evidence with that of tuberculosis. Detection of NTM multiple and extensive drug resistance to the majority of anti-tuberculosis drugs complicates the treatment of the NTM disease. Further study of various aspects of NTM diseases is especially important given the increase in the incidence and prevalence of mycobacteriosis all over the world, challenging differential diagnosis, and detection of NTM extensive drug resistance.

The research protocol on the topic: Study of drug susceptibility of slowly growing nontuberculous mycobacteria (NTM) contains information on sample collection, processing diagnostic material, culture growth, primary differentiation of the isolated culture, and determination of mycobacterial species, drug susceptibility testing of slowly growing nontuberculous mycobacteria prevailing in Moscow region, MICs determination by Sensititre SlowMyco test.

Goal: to investigate efficiency of surgical diagnostics and treatment of pulmonary mycobacteriosis. Materials and methods: 31 patients diagnosed with pulmonary mycobacteriosis underwent surgery. Should mycobacteriosis be not diagnosed before the surgical intervention, the surgery was performed as per standard indications for fibrous cavernous pulmonary tuberculosis or tuberculoma. Results. There were 20 segmental resections, 4 lobectomies (with МАС-, M. kansasii-infection), 5 pneumonectomies (with M. xenopi and M. fortuitum-infection), 2 combined resections. The causative agent was isolated out of surgical specimens in 11 (35.4%) patients; in 10 patients (32.3%) mycobacteriosis was confirmed by detection of non-tuberculous mycobacteria in sputum or bronchial lavage along with the detection of the causative agent in the resected tissue. In the remaining 10 (32.3%) patients non-tuberculous mycobacteria were detected only in sputum and/or bronchial lavage before surgical interventions. Post-surgery complications were observed in 6 (19.4%) of patients, lethal outcome due to myocardial infarction. Clinical cure was achieved in 29 (93.6%) patients.

Scientific and Clinical Antituberculosis Center, Department of Health Care of the city of Moscow, ul. Stromynka 10, Sokol'Niki, Moskva 107014. In 40 patients (with no clinically significant immunosuppression) according to the criteria of the American Thoracic Society, pulmonary mycobacterioses (MAC - 35%, M. kansasii - 25%, M. xenopi - 20%, M. fortuitum - 12,5% и M. chelonae - 7,5%) have been diagnosed. In 95% of patients acute clinical symptomatology with polymorphic radiographic findings has been noted. The constant and massive non-tuberculosis mycobacteria (NTMB) excretion was noted. With fluorescent microscopy acid-fast mycobacteria (AFM) were identified from sputum in 62.5% patients, in 22.5% of patients AFM were found in bronchoalveolar lavage fluid. Cultural analysis of sputum processed by broth dilution method permitted to isolate NTMB in 65%, including in 50% - two times or more. In a solid medium sputum cultures with growth of NTMB were isolated in 45%, including 20% - two times or more. In 10.0% NTMB were isolated when plated on solid media operating material. M. fortuitum, M. chelonae and MAC are the most resistant to anti-TB drugs: M. fortuitum - to all major drugs series, M.chelonae - to all major drugs and a number of reserve drugs, including fluoroquinolones) and MAC (resistant to both isoniazid and rifampicin in 92.9% of cases including, in combination with fluoroquinolones and kanamycin, or capreomycin - in 64.3%)

According to the criteria of the American Thoracal Societypulmonary mycobacteriosis has been diagnosed at 40patients without clinically important immunosupression (MAC--35%, Mkansasii--25%, M. xenopi--20%, M. fortuitum--12.5% and M. chelonae--7.5%). 95% patients have had clinically important symptomatology with polymorphic radiologic development such as a deformation of a lung pattern and focal dissemination (75%), locus and infiltration (52.5%), cavities (42.5%), marked pneumosclerosis (60%) and bronchiectasis (17.5%). 75% patients have had some changes of the bronhial tree. As opposed to tuberculosis the morphology of mycobacteriosis is more homogeneous and includes inflammation with epithelioid giant-cell granuloma and fibrosis, pneumogenic and bronchogenic cavernous cavities, mycobacterial endobronchitis. The polymorphism of clinic-radiologic developments, a similarity of lung diseases morphology caused by nontuberculous mycobacteria makes difficulties to diagnose theirs.

Twenty-five patients with new-onset pulmonary tuberculosis, 52 patients with active sarcoidosis, and 5 healthy donors were examined. Cytokines (IL-2, IL-4, IL-6, TNF-alpha, and gamma-1FN were determined by enzyme immunoassay in the serum and cultured mononuclear supernatant from peripheral blood. IL-2, TNF-alpha, and gamma-IFN) were found in the sera of all the examinees. There were significant differences in the presence of IL-4 that was more commonly detected in sarcoidosis than in tuberculosis (96.2% versus 68%; p = 0.001) and in healthy individuals (40%; p = 0.0001) and in the presence of IL-6 (84.6% in patients with sarcoidosis; 20% in healthy individuals; p = 0.0015; 12% in patients with tuberculosis; p < 0.0001). Supernatant studies showed that IL-4 was absent in 25% of patients with sarcoidosis, nor gamma-IFN in 21.7% of patients with tuberculosis and in 12.5% of patients with sarcoidosis. In tuberculosis, the mean levels of IL-2, IL-4, IL-6, TNF-alpha, and gamma-IFN were greater than those in the control group; but these differences were not statistically significant primarily due to the fact that there was a great scatter of readings. In sarcoidosis, the serum levels of IL-4 (40.9 +/- 38.5 pg/ml) and IL-6 (19.0 +/- 2.7 pg/ml) were significantly higher than those in healthy individuals (p = 0.01 and p = 0.026, respectively) and in patients with tuberculosis (p = 0.0005 and p < 0.0001). The supernatant from patients with tuberculosis showed no significant differences in the content of cytokines than that from donors. In patients with sarcoidosis, the increase in the level of TNF-alpha (757.8 +/- 142.8 pg/ml) was statistically significant, as compared with the controls (p = 0.036) and patients with tuberculosis (p = 0.018), so as that of gamma-IFN (272.9 +/- 58.0 pg/ml), as compared with patients with tuberculosis (p = 0.046). Thus, the serum levels of IL-6 and IL-4 and the capacity of monocytes and macrophages for synthesizing TNF-alpha and gamma-IFN may be used as an auxiliary criterion for the nosological diagnosis of sarcoidosis and tuberculosis.

The specimens of biopsy of the lung and lymph nodes from 24 patients with sarcoidosis were immunophenotyped. The monoclonal antibody panel for immunophenotyping the monocyte-macrophage cells included HLA-DR, CD64, CD163; CD7, CD3, CD4, CD8, HLA-DR, and CD20 were used to assess lymphocytic populations. In sarcoidosis, the majority of cell elements of a granuloma are in a state of activation, as evidenced by HLA-DR expression on the epithelioid, giant cells, T lymphocytes (which was observed in more than in 90% of cases), the extent of this expression decreasing as fibrosis develops. There is a statistically significant correlation between the presence of individual lymphocytic subpopulations and monocyte-macrophage cells in the granuloma. No clear relationship of the phenotype of a granuloma to the clinical form (stage) of sarcoidosis suggests that is based on the common self-sustaining process of formation, functioning, and involution of granulomas, which has no direct agreements in the X-ray and laboratory manifestations of the disease.