ЭПИДЕМИОЛОГИЯ ТУБЕРКУЛЕЗА
The aim was to assess the risk of pulmonary tuberculosis development in patients with comorbid bronchopulmonary pathology living in rural areas.
Materials and methods. The retrospective study included 268 patients with newly diagnosed pulmonary tuberculosis (TB); in 44 cases there was a combination of TB and chronic bronchopulmonary diseases (BPD). The median population of Omsk district of Omsk region for 5 years was 78325 people (IQR 77 768 – 78 388), of which persons with BPD constituted 8.5% (median – 2191 cases, IQR 2143 – 3321). The odds ratio (OR) and its 95% confidence interval (95% CI) were calculated for disease risk assessment.
Results. The risk of TB was significantly increased in individuals with BPD compared to the rest of the population (OR = 24.06, 95% CI 17.26-35.56, p < 0.001). Maximum risk of disease was associated with chronic obstructive pulmonary disease (OR = 53.86, 95% CI 36.67-9.11, p < 0.001); bronchial asthma increased the odds of developing TB to a lesser extent (OR = 2.78, 95% CI 1.47-5.24, p < 0.001). The leading additional factor according to the results of factor analysis was the presence of addictions (smoking, past or present substance use). TB contact in this category of patients was either not established or had been previously in penitentiary institution; TB detection occurred when patients sought medical care for reasons unrelated to respiratory pathology.
DIAGNOSIS OF TUBERCULOSIS
The aim of the study was to investigate computed tomographic signs of destructive forms of tuberculosis and nontuberculous mycobacterioses of the lungs.
Materials and methods. Сomputed tomography data were analyzed in 154 patients with destructive forms of tuberculosis (78 patients) and nontuberculous mycobacterioses of the lungs (76 patients); the diagnosis was confirmed by isolation of Mycobacterium tuberculosis or various nontuberculous mycobacteria identified by microbiological methods to species in the diagnostic material.
Results. Тhe CT picture in tuberculosis was more characterized by irregular-round shape of caverns (57.8%), vagueness of their external contour, multiple destructions (47.4%), infiltration of the adjacent pleura (83.3%); the thickness of the cavity wall and pericavitary infiltration more often exceeded 1 cm. In non-tuberculous mycobacteriosis, solitary cavities of irregular-oval shape, with thin walls (less than 5 mm) with calcinosis (40,8%), clear external contour (82,9%), open bronchocavitary joints (in 81,6% of cases) were more often detected; bronchiectasis (92,1%), hyperinflation and fibrosis, foci of bronchogenic dissemination were more frequent in the surrounding lung tissue.
Conclusion. Сareful analysis of CT semiotics of destructive forms of tuberculosis and pulmonary mycobacteriosis contributes to the efficiency of differential diagnosis and routing of patients with these diseases.
The aim of the study was to determine the levels of sensitivity to itraconazole in 51 species of opportunistic fungi isolated from tuberculosis patients in the diagnosis of bronchopulmonary and disseminated mycoses.
Materials and methods. The sensitivity levels to itraconazole of 902 clinical strains of yeast fungi from the genera Candida (14 species), Cryptococcus (3 species), Geotrichum (1 species) were determined, Hanseniaspora (1 species), Saccharomyces (1 species), Saprochaete (1 species), Rhodotorula (2 species), Trichosporon (1 species) and mycelial fungi from the genera Acremonium (1 species), Alternaria (1 species), Aspergillus (12 species), Aureobasidium (1 species), Cladosporium (1 species), Curvularia (1 species), Fusarium (3 species), Paecilomyces (2 species), Penicillium (2 species), Rhizopus (1 species), Trichoderma (2 species), isolated from tuberculosis patients with suspected bronchopulmonary and disseminated mycoses in the Moscow Research and Clinical Center of Tuberculosis Control in the period 2012–2024.
Results. Testing revealed high activity of itraconazole against pathogens of candidiasis (except C. glabrata), cryptococcosis, aspergillosis (except A. ustus), pheohyphomycosis (genera Alternaria, Aureobasidium, Cladosporium, Curvularia), rare yeast mycoses (genera Geotasidium, Aureobasidium, Curvularia). ustus), pheohyphomycoses (genera Alternaria, Aureobasidium, Cladosporium, Curvularia), rare yeast mycoses (genera Geotrichum, Hanseniaspora, Saccharomyces, Saprochaete, Trichosporon), hyalohyphomycoses (genera Penicillium, Trichoderma). The activity of itraconazole was low against the pathogens Fusarium spp., Rhodotorulosis (Rhodotorula spp.), Zygomycosis (Rhizopus arrhizus) and variable against two hyalohyphomycetes Paecilomyces variotii and Acremonium strictum.
Aim. To study the susceptibility of clinical strains of M. tuberculosis complex (MTB) to delamanid using the automated Bactec MGIT system.
Material and methods. We studied 79 M. tuberculosis isolates from 78 TB patients treated in 2017-2023. 39 MTB strains were susceptibile and 40 had different drug resistance profiles to anti-tubercular drugs. Minimum inhibitory concentrations (MIC) of delamanid in Middlebrook 7H9 liquid medium were determined using the Bactec MGIT system, the susceptibility results were assessed using the critical concentration of 0.06 μg/ml recommended by WHO. Whole genome sequencing was used to identify mutations associated with phenotypic resistance to delamanid in MTB strains.
Results. Delamanid demonstrated high activity against drug-naive MTB strains. MIC values ranged from 0.004 to 0.03 μg/ml for 97.4% (76/78) of studied susceptible MTB strains. Two MTB strains isolated from newly diagnosed patients with pulmonary TB had primary resistance to delamanid (2.6%; 2/78), and acquired resistance was detected in one MTB strain (2.6%; 1/39) during delamanid-based therapy for drugresistant TB. Genetic determinants of resistance were detected in three clinical MTB strains (N91T and W88* mutations in the ddn gene and Q299* mutation in the fgd1 gene) with MICs exceeding the critical concentration.
TUBERCULOSIS TREATMENT
The aim of the study is to improve the effectiveness of treatment of patients with pulmonary tuberculosis by correcting autonomic dysfunction and reducing the volume of residual post-tuberculosis changes using dioxomethyltetrahydropyrimidine.
Material and methods. The continuous prospective study included 70 healthy individuals (comparison group) and 77 tuberculosis patients (observation group) divided into 2 subgroups: 41 patients received only antituberculosis drugs, 36 received dioxomethyltetrahydropyrimidine in the adaptogen regimen as part of complex treatment. The presence and nature of autonomic dysfunction were assessed using heart rate variability study; the volume of residual lung changes formation during treatment and its relationship with autonomic dysfunction were analyzed.
Results. The predominant influence of sympathetic nervous system with centralization of organism regulation more than 2 times more often than in healthy individuals was observed in tuberculosis patients. When assessing the state of the body regulatory systems during treatment and radiological outcomes of tuberculosis process, 77.3% of patients showed moderate functional tension and adaptation failure according to the activity index of regulatory systems, combined with the formation of pronounced residual tuberculous changes. Addition of dioxomethyltetrahydropyrimidine to antituberculosis therapy promoted the recovery of vegetative dysfunction. The correlation between restoration of autonomic function and reduction of formation of large residual tuberculous changes in lungs of tuberculosis patients was revealed (p < 0,001).
The aim of the study was to analyse the results of adjuvant therapy with glutamyl-cysteinyl-glycine dinatrium as part of the complex treatment of patients with MDR, pre-XDR and XDR tuberculosis.
Materials and methods. The results of the intensive phase of treatment of 40 patients were analysed; the first group (main) included 17 patients receiving antituberculosis chemotherapy in combination with glutamyl-cysteinyl-glycine sodium (Glutoxim), the second group (control) included 23 patients receiving only chemotherapy.
Results. The study showed the effectiveness of the use of glutamyl-cysteinyl-glycine dinatrium (Glutoxim) in the form of a reduction in the elimination of intoxication symptoms and clinical manifestations, better rates of bacterial conversion (100% vs. 39.1% in the control group in the first 3 months of treatment, p<0.01) and achievement of positive radiological dynamics (100% vs. 52.2% after 4 months of treatment). The use of Glutoxime helped to reduce the frequency (17.6% in the main group vs. 43.5% in the control group, p=0.085) and duration (55.5 vs. 90 days, p=0.017) of adverse reactions to anti-TB drugs, normalisation of of liver function tests.
The aim was to evaluate the efficacy of glutoxime in achieving haematostimulating, detoxifying and abacilliating effects in the treatment of tuberculosis based on clinical and laboratory data.
Materials and methods. The study included 120 patients with newly detected destructive pulmonary tuberculosis aged 42.8±3.2 years (25-55 years); the main group consisted of 90 patients who received glutoxime 60 mg intramuscularly once a day for 10 days, then 60 mg every other day for 20 days with standard antituberculosis chemotherapy. The control group was formed of 30 first-diagnosed patients with pulmonary tuberculosis who received chemotherapy without glutoxime. We evaluated the dynamics of the calculated leucocytic index of intoxication according to Y.Y. Kalf-Kalif as an indicator of the level of endogenous intoxication after 30 days of treatment.
Results. In a month from the beginning of treatment normalization of hematological parameters was noted in 86,7% of patients of the main group and 60% of the control group (p=0,002). Leukocytic index of intoxication in the patients of the main group receiving glutoxime decreased 6 times in comparison with the initial one. The achieved values were significantly lower compared to the control group (0.47±0.18 and 1.83±0.21, p≤0.05). The number of TB patients with sputum smear negativation in the main group after 1, 2 and 3 months of treatment was higher compared to the control group (differences were statistically insignificant). Conclusion. The use of Glutoxime in pathogenetic therapy of destructive tuberculosis provides a significant decrease in the laboratory index of endogenous intoxication.
LITERATURE REVIEW
Therapeutic drug monitoring (TDM) is one of the most promising technologies for personalized tuberculosis therapy, which can significantly improve the efficacy and safety of treatment in the most complex categories of patients. The applied goal of TDM is to optimize doses of TB drugs based on the control of their serum concentrations during treatment.
The review considers the basic principles, definitions and parameters of TLM, current indications for testing, methods of data collection, analysis and interpretation from the perspective of a practicing phthisiatric physician; analysis of the evidence base is presented. The target populations for implementation of TLM are patients with HIV infection, diabetes mellitus, other severe multicomorbid pathology; pediatric and elderly patients, with delayed response to treatment and high risk of severe adverse reactions.
For effective implementation of TLM it is necessary to conduct controlled studies to assess its clinical and economic results, to develop methods to increase the availability of this technology for the maximum number of TB institutions.
ТЕЗИСЫ XII ЕЖЕГОДНОЙ КОНФЕРЕНЦИИ МОСКОВСКИХ ФТИЗИАТРОВ
ISSN 2413-0354 (Online)