Treatment of patients with multidrug­resistant and extensively drug resistant tuberculosis depending on the composition of individualized regimens: immediate and long­term results

Objective — to study the effectiveness of treatment of MDR-TB (multidrug-resistant tuberculosis) and preXDR-TB/XDR-TB (pre-extensively and extensively drug resistant tuberculosis), depending on the composition of ITRs (individualized treatment regimens). Materials and methods. Тhe prospective observational study included 566 patients with MDR/preXDR-TB and XDR-TB during 2016—2020 on the scientific clinical bases of the SI «National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine» and ME «Kryvyi Rih Anti-tuberculosis Dispensary» Dnipropetrovsk Regional Council Department. Patients were prescribed individualized treatment regimens in cases where short (standard or modified) regimens could not be prescribed. Patients were divided into comparison groups: 469 of them were treated with antimycobacterial therapy including bedaquiline and other effective antimycobacterial drugs groups A—C (without delamanid) — group 1. And 97 patients who were treated with the inclusion of both new antimycobacterial drugs (bedaquiline and delamanid) — group 2. Results and discussion. Regardless of whether the delamanid, in addition to bedaquiline and other drugs selected for the scheme according to WHO recommendations, «effective treatment» was found in 91.3 against 88.6 % of patients. In the remote period (6-month — 4-year follow-up period) there was no recurrence of the disease, regardless of the composition of the regime. The loss of treatment effectiveness was due to deaths from non-tuberculosis reasons and those lost for follow-up. Conclusions. For highly effective treatment, individualized regimens should include bedaquidine and linezolid from group A, and for previously ineffectively treated patients, clofazimine and carbapenems must be included (possibility to include 4 or more effective AMDs in ITR). For patients with fluoroquinolone resistance, treatment should include delamanid.

Presentation and implementation of the results of the own scientific research — a practical approach

During postgraduate studies, future PhDs must master a wide range of teaching and research skills that meet global and European academic standards. In particular, candidates for the degree of Doctor of Philosophy must acquire theoretical knowledge that is sufficient to produce new ideas, solve complex problems in the field of professional and/or research and innovation, acquire universal research skills, including oral and written presentation of their own scientific results, application of modern information technologies in scientific activity, organization and carrying out of educational employments, management of scientific projects and/or introduction of offers concerning financing of scientific researches, registration of the intellectual property rights. Objective — to summarize information about the relevance of the discipline «Presentation and imple­mentation of the results of the own scientific research» and highlight practical approaches to its teaching. Materials and methods. Analysis and generalization of information on current documents governing the educational process for applicants for the degree of «Doctor of Philosophy» in medical specialties, and literature sources on the presentation and implementation of dissertation research. Results and discussion. The discipline «Presentation and implementation of the results of the own scientific research» is an important component of the preparation of graduates of the degree of Doctor of Philosophy in the field of knowledge 22 «Health». As part of the study of this discipline, students learn the concept of innovation process and innovation of the scientist, get acquainted with the basics of protection of the results of their own research and modern aspects of patent information search technologies, gain skills in presenting the results of the own research using various forms of new information technologies and implementation in the practice of health care and educational process of the results of the own research. Conclusions. Assimilation of theoretical material and practice of the practical part of the program of the discipline «Presentation and implementation of results of the own scientific research» provides acquisition by postgraduate students of corresponding integral, general and special competences and formation of integrative final program results of training necessary for further professional activity of the future doctor of philosophy.

Epidemiological trends in tuberculosis in Ukraine at the beginning of the COVID­-19 pandemic

Objective — to examine the tendencies of the epidemiological situation on tuberculosis in Ukraine at the beginning of the COVID-19 pandemic in 2020. Materials and methods. The analysis of the data of official statistics in 2015—2020, a survey of 157 medical experts and a telephone questionnaire survey of 69 residents of the Volyn region. Results and discussion. It was established that the disease of COVID-19 has found its imprint on the epidemiological situation of tuberculosis and on the functioning of the TB care service. In 2020, the rate of decline in the incidence of pulmonary and extrapulmonary tuberculosis was significantly more intensive than in previous years. However, the incidence of tuberculosis among contacts with bacterial excretion in tuberculosis foci increased 1.85 times in each year. The frequency of tuberculosis recurrences is steadily decreasing.The prevalence and mortality from all forms of active tuberculosis among the entire population of Ukraine has a tendency similar to a decrease in morbidity.The effectiveness of treatment of patients of all categories is proportional to the severity of the tuberculosis process, but still insufficient. Mortality in TB care institutions increased in the previous year against the decrease of this indicator in previous years. Against the background of the inaccessibility of the population to TB care, day hospitals are underused, and the sanatorium network needs to be reorganized. The surgical method of treatment of patients is extremely insufficiently realized. Conclusions. The dispensary contingent of TB care institutions is decreasing every year. There is a reduction in the infrastructure of the TB care service, and in each year, the largest reduction was in the bed stock of TB care institutions and sanatoriums, as well as a decrease in the number of TB doctors.

Comparative characteristics of the epidemiological situation of chemoresistant tuberculosis in Germany and Ukraine

Objective — to compare the epidemiological situation of chemoresistant tuberculosis in Germany and Ukraine, in addition analyzing the nature and features of chemoresistant tuberculosis in 192 patients treated at the Ternopil Regional TB Dispensary Ukraine during 2017—2018. Materials and methods. In order to study the comparative characteristics of the epidemiological situation with chemoresistant tuberculosis in Germany and Ukraine, modern literature sources were used with the search query «epidemiological situation with chemoresistant tuberculosis in Germany», «epidemiological situation with chemoresistant tuberculosis in Ukraine». Separatelly a retrospective cohort study was conducted. The nature and features of the course of chemoresistant tuberculosis in 192 patients who were treated in the Ternopil Regional TB Dispensary during 2017—2018 were analyzed. Results and discussion. Analysis of literature sources showed that multidrug resistant Tuberculosis (MDR-TB) is relatively seldom in Germany with around 100 cases annually. Overall, the epidemiological situation of MDR-TB has been stable since the beginning of the statistical recording of the disease in 2002. In 2013, the highest proportion of MDR TB was registered at 3.3 %. Detailed analysis of notifi cation data shows that the tuberculosis situation in Germany is mainly influenced by migratory movements and demographic changes in the population. Despite the positive overall epidemiological trend with decreasing incidence rates, however, the burden of TB in Ukraine remains significant. According to the latest WHO estimates for 2018, TB incidence in the country(new cases and relapses) is the 4th highest among 53 countries of the WHO European Region.To address the situation, reduce TB prevalence, scale up TB early detection and diagnosis, and ensure effective treatment, Ukraine adopted, in 2019, the 2020–2023 State Strategy for Development of Anti-Tuberculosis Care for the Population.The analysis performed of 192 patients of the MDR/XDR-TB Cohort from the TB-Dispensary Hospital in Ternopil (Ukraine) from 2017—2018, showed that the resistanse of mycobacteria to anti-TB drugs was dominated by cases of MDR-TB — 57.3 %. Among patients first diagnosed were 52.6 %, relapses were 46.4 %. Destruction in the lungs was detected in 71.9 %. 111 patients (57.8 %) had treatment success, and 81 (42.2 %) had poor treatment outcomes or were lost to follow-up. Conclusions. The epidemiological situation of tuberculosis in Germany is stable and improving. Despite the positive overall epidemiological trend, the burden of TB in Ukraine remains significant. In 2018, TB incidence in the country (new cases and relapses) was 80 per 100 thousands population. In Ukraine during the period (2015—2018), the proportion of «pre-XDR» and XDR cases increased from 47.4 to 51.3 %. Among patients with chemoresistant tuberculosis, MR TB predominates (57.3 %), with destruction in the lungs and only 57.8% are effectively treated.

Influence of outpatient treatment newly diagnosed pulmonary tuberculosis on the development of familial tuberculosis (epidemic situation)

The incidence of tuberculosis in our country, according to statistics, seems to be declining. However, it should be remembered that the figures of the Crimean Autonomous Republic and the temporarily occupied territories of Donetsk and Luhansk oblasts are excluded from the digital data. Of particular concern are the significant worldwide morbidity and infant mortality rate of 700 people per day.The problem’s urgency is due to the data and the increase in the number of patients with common and destructive forms of pulmonary tuberculosis. The leading factor is the constant increase in the number of patients with multidrug­resistant conditions, the effectiveness of treatment of which does not reach 50%. In comparison, the WHO considers the critical limit for stabilizing the epidemic situation «effective treatment» at 85 %. Objective — to study the features of familial tuberculosis on the background of outpatient treatment of patients with newly diagnosed tuberculosis. Materials and methods. We observed 157 families with various forms of pulmonary tuberculosis. Radiation, bacteriological, immuno­genetic methods were used in the examination. Family members were examined every six months. Results and discussion. Among the TB contacts after this period, tuberculosis was found in 162 people. Sources of tuberculosis (157) were bacillary in 49.7 %, TB contacts — in 43.8 %. Among patients in the group of heads of tuberculosis, there were 28 (35.9 %) people on MRTB, and in the group of TB contacts — 32 (45.1 %), р < 0.05. Thus, tuberculosis’s cause in TB contacts was not isolated from the family of patients with newly diagnosed tuberculosis. Conclusions. Based on the results obtained, it is safe to say that if at least fixed bacillary patients were hospitalized, there could be no family TB contact patients. Comparing all sources of tuberculosis patients (157), it can be imagined that cases of familial tuberculosis (162) could be avoided. Nature «responded» to ignoring one part of the epidemic process (transmission of infection that increases with contact) by increasing the number of patients with familial tuberculosis by 5 people. We note: it was only about the Sumy region and only for a limited time.

The effectiveness of immunoglobulin G application in patients with drug­-resistant tuberculosis/HIV with CD4+ lymphocytes from 200 to 50 cells/µl according to biochemical data

Objective — to study the effectiveness of immunoglobulin therapy in patients with co-infection of drug-resistant tuberculosis (DR-TB)/HIV at the level of CD4+ lymphocytes from 200 to 50 cells/μl, based on a study of the dynamics of biochemical parameters. Materials and methods. The study involved 52 patients aged 20 to 55 years, with a mean age of (37.2 ± 7.8) years. All patients were HIV-positive with laboratory-confirmed DR-TB with mycobacterial resistance to first- and second-line drugs. Patients with DR-TB/HIV were distributed as follows: 1 group (control) — 26 patients with DR-TB/HIV, receiving standard treatment of second-line AMBP and ARVT; group 2 (main) — 26 patients with DR-TB/HIV, who also received standard treat­ment of second-line AMBP and ARVT, with the addition of complex therapy with intravenous immunoglobulin G (IgG). Results and discussion. Against the background of treatment, the dynamics of changes in biochemical parameters was as follows: patients in the control group, after the first 2 weeks of AMBP, there was an increase in intoxication load on the hepatobiliary and urinary systems, which led, on the one hand, to dysfunction liver with hyperbilirubinemia, increased transaminase activity, thymol turbidity, and on the other — to the development of renal failure with hypercreatininemia, hyperuricemia, azotemia and oliguria. As a result, timely appointment of ARVT (2 weeks after AMBP) in 19 (73.1 %) patients was impossible and was carried out much later than desired (after 2—3 months).Treatment of patients with comorbid pathology of DR-TB/HIV, which included complex intravenous IgG on the background of complex therapy, was accompanied by positive clinical and laboratory dynamics, which created conditions for ARVT involvement after the second week of complex therapy according to the developed treatment method. Conclusions. The use of immunologically targeted treatment with intravenous IgG made it possible to successfully prescribe ARVT to patients of the main group in 2 weeks from the start of AMBT, which is very useful to prevent adverse reactions, increase treatment efficacy and reduce mortality in patients with comorbid DR-TB/HIV in a state of deep immunosuppression.

Surgical treatment of broncho­­pulmonary purulent­inflammatory complications due to permanent coronaviral ihfection — the first experience

Objective — to acquaint doctors of different profiles with thoracic pathology in patients with coronavirus infection. Materials and methods. Since the beginning of the SARSCoV-2 pandemic, on the basis of the clinical department for the surgical treatment of tuberculosis and NZL complicated by purulent septic infections 70 patients were treated, of which 39 (55.7 %) had various broncho-pulmonary purulent-inflammatory complications of coronavirus infection. Results and discussion. The distribution of treated patients with bronchopulmonary purulent-inflammatory complications of coronavirus infection by nosology is presented in Table 1. According to the table presented, pleural empyema was a frequent bacterial complication of the respiratory system — 18 (46.1 %) cases; only 6 (33.3 %) patients were diagnosed with broncho-pleural communication, while in 12 (66.7 %) patients, already at the stage of hospitalization, a functioning broncho-pleural fistula was observed.17 (94.4 %) patients with empyema underwent videothoracoscopic (VATS) debridement of the pleural cavity with polydrainage and the use of prolonged active aspiration in the postoperative period. The management of such patients was no different, except for 2 points: the need to continue GCS therapy and the obligatory long-term prescription of anticoagulants and antiplatelet drugs.In 1 (5.6 %) case, due to the extremely serious condition of the patient, only drainage of both pleural cavities was performed (this case was fatal). In another case, after 2 VATS of the pleural cavity, bronchial blocking of the upper lobe and intermediate bronchi of the right lung was performed, followed by active aspiration. Nonspecific exudative pleurisy was diagnosed in 8 (20.5 %) patients after coronavirus infection. There were 13 patients with abscess pneumonia and abscesses (33.3 %). This group of patients underwent drug therapy for a long time, which consisted in the appointment of broad-spectrum antibiotics, anticoagulants, pathogenetic therapy and symptomatic treatment.After a course of conservative treatment, 9 (69.2 %) patients underwent the following surgical interventions — sublobar resection for a sanitized lung abscess in 4 (44.5 %) cases, lobectomy in the presence of sanitized residual large cavities in 3 (33.3 %) patients, partial pleurectomy with decortication of the lung and sublobar resection of the lower lobe of the left lung in 2 (22.2 %) patients.Conservative therapy was successful only in 4 (30.7 %) patients. All 13 patients with abscess pneumonia and abscesses were discharged from the institute with full recovery or improvement (small sanitized destruction cavities up to 2 cm in diameter remained in the lung parenchyma). There were no lethal outcomes.The overall effectiveness of the treatment of this contingent of patients was 97.4 %, and the general mortality rate — 2.6 %.Videothoscopic treatment was effective in 25 (64.1 %) patients with pleural empyema and nonspecific pleurisy, and in 4 (16 %) patients it allowed to stabilize the condition and carry out resection surgery. Conclusions. Purulent-destructive complications of the respiratory system in coronavirus infection have a causal component, and therefore timely exposure to all parts of the pathogenesis can significantly reduce their level. Preference should be given to videothoracoscopic intervention in the complicated course of coronavirus infection. The high level of diagnosis (25.4 %) of concomitant pathology of the chest with the widespread use of radiological methods in the pandemic of coronavirus infection may indicate a low level of preventive medicine in the state.

Complications of invasive methods diagnosis of pulmonary dissemination syndrome, their prevention and treatment

Objective — to study the possible complications that arise when using invasive methods for the diagnosis of pulmonary dissemination syndrome, to develop measures aimed at their prevention and treatment. Materials and methods. Data from 216 patients who used invasive methods to diagnose pulmonary dissemination syndrome were analyzed. Patients were divided into 3 groups, depending on the type of biopsy: Group I — 143 patients who underwent VATS lung biopsy, Group II — 64 patients who underwent endobronchial ultrasound transbronchial biopsy lungs (EBUS TBBL); Group III — 9 patients who underwent open biopsy. Complications in I — 12 (8.4 %), II — 5 (7.8 %), III — 2 (22.2 %), total — 19 (8.8 %). These were lung tear, wound suppuration, disease progression, pneumothorax, hemoptysis, respiratory failure, intrapleural hemorrhage. Results and discussion. Based on the obtained data, we have proposed methods of prevention of complications: radiography of the thoracic cavity in the first day after biopsy; correction of antiplatelet therapy; careful selection of patients for biopsy taking into account age, concomitant pathology, taking drugs, history.Conclusions. Lung biopsy for pulmonary dissemination syndrome is a safe type of diagnosis with a low level of complications — 8.8 %.The least traumatic method is transbronchial lung biopsy under ultrasound control.If it is impossible to perform a transbronchial lung biopsy, or if the obtained material is uninformative, the next step is to use a video­assisted lung biopsy.An open biopsy should be considered last and only under strict indications.It is important to choose the right method of biopsy, taking into account age, history, drugs.