Modern treatment regimens for tuberculosis with multiple and broad drug resistance (MDR/XDR) of the pathogen provide for the simultaneous administration of several drugs with a proven cardiotoxic effect in the form of prolongation of the QTc interval and provocation of life-threatening arrhythmias. In conditions of the spread of cardiovascular and other comorbid pathology, it is important to assess the risk of cardiotoxic reactions and ensure the safety of patients during the entire course of treatment. The aim of the study was to assess the degree and risk of prolongation of the QTc interval in tuberculosis patients with MDR/XDR pathogen, including concomitant cardiological pathology, against the background of treatment regimens with the inclusion of bedaquiline. Materials and methods of research . The retrospective study included 185 tuberculosis patients with MDR/XDR of the causative agent: 70 people with cardiovascular pathology (except decompensation of heart failure, bradyarrhythmias, ventricular arrhythmias and QTc prolongation in the anamnesis) and 115 people. without it, who received chemotherapy with the inclusion of bedaquiline and fluoroquinolones. The dynamics of clinical symptoms and ECG were evaluated against the background of treatment. Risk factors for cardiotoxic reactions were determined using the method of multiple logistic regression. The results of the study . Prolongation of the QTc interval was observed in 58 people (31.4%, 95% CI 25.1–38.4%), clinically significant (more than 500 ms, 60 ms or more from the baseline, with ventricular arrhythmia) – 4.3%; bradycardia – 3.8%, cardialgic syndrome – 8.1%. Risk factors for prolongation of the QTc interval were the presence of any cardiovascular disease (OR 2.33, 95% CI 1.23-4.41), simultaneous administration of three or more drugs that can lead to QTc prolongation (OR = 3.31, 95% CI 1.73–6.32), clarithromycin administration (OR = 4.01, 95%CI 1.4710.97), the number of points on the Tisdale scale is more than 6 (OR = 3.42, 95% CI 1.78–6.62). Conclusion . Prolongation of the QTc interval is a common adverse reaction in the treatment of tuberculosis with MDR /XDR pathogen, clinically significant in 4.3% of cases. The use of a standard ECG monitoring scheme is justified; it is necessary to avoid prescribing three or more drugs that affect the QTc interval to patients with any cardiovascular pathology with a Tisdale score of more than 6 points.

The experience of the centralized control of the appointment and implementation of chemotherapy regimens for MDR/XDR TB by subcommittee of the head TB-physicians board of the Moscow Scientific and Practical Center for Tuberculosis Control in 2014-2021 presented. Totally, 6023 cases considered, 30% – primary diagnosis and treatment, 70% – monitoring of treatment. As a result of measures carried out under centralized control, the number of patients with respiratory MDR/XDR TB decreased by 4 times: from 752 in 2011 to 189 in 2021, mainly due to the cure of patients. There was a significant increase in the effectiveness of treatment of patients with MDR/XDR TB: in the 2013 cohort, the effective treatment courses was 45.9%, in the 2018 cohort. – 69.6%, while there was a decrease in the proportion of ineffective courses by almost 2 times – from 14.0 to 7.9%, a decrease of interrupted treatment by more than 2 times – from 12.2% to 4.8%, a decrease in the proportion of deaths from tuberculosis by 3 times – from 8.7% to 2.8%. The main difficulties of implementing new regimens of MDR/XDR TB chemotherapy have also been identified. The presence of comorbidity prevents the appointment of at least one of the most effective anti-tuberculosis drugs (bedaquiline, linezolid, moxifloxacin, cycloserine) in at least 25% of patients. The frequency of adverse events (AE) in MDR/XDR TB patients was 2nd stage severity was 33.2%, 3-4 stage – 5.3%. Correction of chemotherapy regimens with the exclusion and/or replacement of anti-tuberculosis drugs was necessary due to AE in general in 52.5% (95% CI 41.7-63.1%) of patients, and in 2.5% of cases chemotherapy was canceled completely, for a period of a week to 1.5 months. In at least 20% of patients, an important task is to ensure proper adherence of the patient to treatment, which requires counseling by a psychologist.

In order to comparatively assess the amount of costs for the relief of the most common adverse reactions (AE) in different treatment regimens of patients with tuberculosis with multiple and broad drug resistance (MDR and XDR) of the causative agent, an analysis of the frequency, spectrum, severity and cost of relief of all AE developed against the background of chemotherapy of 239 tuberculosis patients with MDR, divided into three groups: I – 82 patients treated in 2011-2015 using only anti-tuberculosis drugs (ATD) of the main and reserve series; II – 77 patients in whom, in addition to these ATD, linezolid was included in the treatment regimen; III – 80 patients treated with linezolid and bedaquiline with ATD of the main and reserve series. The cost–effectiveness analysis used to identify the most economically effective chemotherapy regimen.Results. 564 AE episodes were registered in 220 patients (92.1%, 95% CI 87.9–94.9%), without significant intergroup differences (92.7%, 96.1% and 87.5%, respectively, in groups I, II and III, p > 0.05). AE III–IV degrees of severity were observed in 35 patients (14.6%, 95% CI 10.7–19.7%); no significant differences in severity and frequency of individual types of AE were found. The elimination of myelo-, hepato- and cardiotoxic reactions of III-IV severity required the greatest costs. The cost of cupping all AE and the cost-effectiveness ratio were the lowest in group III patients (CER = 28.9 thousand RUB compared to 41.7 thousand rubles and 40.3 thousand rubles in groups I and II, respectively).Conclusion. Тhe use of tuberculosis chemotherapy regimens with MDR /XDR pathogen with the inclusion of bedaquiline and linezolid requires the lowest total costs for the relief of adverse reactions with comparable effectiveness

The objective: safety assessment of chemotherapy regimens compiled in accordance with the recommendations of World Health Organization (WHO), 2019, in patients with multiple drug resistant tuberculosis (MDR) in clinical practice settings.Subjects: Frequency, patterns, severity and risk factors of adverse events (AE) of chemotherapy regimens compiled in accordance with the WHO recommendations as of 2019 were analyzed in 122 patients with MDR and XDR respiratory tuberculosis within programmatic use of new anti-tuberculosis drugs.Results. The frequency of AE made 64.8% (95% CI 55.9-72.7%), gastrointestinal, cardiovascular and allergic events prevailed, the comorbidity was the risk factor of AE development (OR 6.44; 95% CI 1.91-21.76). AEs of with severity degrees 3-4 were observed in 24.6% (95% CI 17.8-33.0%), neurotoxic, ototoxic and hepatotoxic reactions prevailed; risk factors included female sex (OR 3.15, 95% CI 1.32-7.53) and complications of chemotherapy in the past (OR 3.50%, 95% CI 1.49-8.70). At least one anti-tuberculosis drug was canceled due to AE in 26.2% (95% CI 19.2-34.7%), and any of Group A drugs was canceled during the first 6 months of chemotherapy in 13.9% (95% CI 8.8-21.3%) of patients.