Experience of using mCRL in patients with drug-resistant TB and evaluation of treatment effectiveness and adverse effects

Abstract

Objective. To study the frequency of adverse events when using new drugs in the treatment regimen for patients with MDR-TB and evaluate the effectiveness of new shorter regimens. Material and methods of research. New shortened regimens have been used for the treatment of patients with MDR- TB since September and February 2020 in two institutions (MJ and GS). 225 MDR cases were identified in the treatment regimens, Bdq, Lzd, Lfx, Cfz, Cs were prescribed to 106 patients. Gender balance: men 58 (67.4%), women 28 (32.56%).Almost 67 (79.76%) patients had a bilateral process with decay cavities, and 17 (20.24%) patients had a process without decay. The main side effect of bedaquiline is cardiotoxicity, which manifests itself in prolongation of the QT interval and an increase in QTcF (Fridericia coefficient) calculated using the Fridericia formula. The cardiotoxicity of bedaquiline persists after taking it for another 6 months, i.e. has a cumulative effect. In this connection, with the use of bedaquiline in treatment regimens, an electrocardiographic (ECG) study is initially performed. When monitoring treatment with bedaquiline in the first month, an ECG study is performed after 14 days, before the end of the course of treatment is carried out monthly, after the end of the course for 3 months. SAEs were identified in 3 patients. Hypokalemia, myelosuppression and hyperglycemia were noted accordingly in the 1 patient Peripheral neuropathy (moderate) was observed in 7 patients.Results. Culture conversion was observed in 63 patients (75%) who took Bdq, Lzd, Lfx, Cfz, Cs treatment regimens for 9 months. Time to culture conversion was ≤ mean (or median) in 10 (25%) cases, ≥ mean (or median) in 97 (75%) cases In the remaining 16 (18%) patients, the isolation of mycobacteria persisted, and additional detection of resistance to the main drugs provided a rationale for prolonging the course of treatment. In 5 patients dropped out, these patients were discharged for violations of the nosocomial regimen and took drugs only from 28 days to 2 months. There was no prolongation of the QT interval (0.48-0.51 s). All continued the course with bedaquiline. Peripheral neuropathy (moderate) occurred in 7 (8%) patients taking linezolid. All patients (with mild neuropathy) continued the course with linezolid. These patients were prescribed pyridoxine until the end of the regimen. Myelosuppression was observed in 59 patients. 10 of them had grade 1, 3 had grade 2, and only 1 had grade 3 myelosuppression. Nearly all of those treated with clofozemin had a dark brown skin tone. Treatment outcomes and course completion were 63(75%), failure 16(19%). Conclusion. The effectiveness of shortened treatment regimens for MDR/TB patients with the inclusion of new anti-TB drugs (Bdq, Lzd, Lfx, Cfz, Cs) in the treatment regimen turned out to be quite high, side effects were eliminated in time with the help of careful monitoring. In earlier terms, sputum conversion and closure of decay cavities were noted.