Efficacy of using bedaquiline in treatment of tuberculosis patients with multiple and extensive drug resistance

Abstract

The objective: to compare treatment efficacy of pulmonary tuberculosis patients with multiple (MDR) and extensive drug resistance (XDR) using a standard chemotherapy regimen and the regimen containing bedaquiline.Subjects and Methods. A retrospective study was conducted to analyze treatment outcomes in 219 patients with pulmonary tuberculosis and MDR/XDR of Mycobacterium tuberculosis (MTB) aged 18-75 years old who were treated in in-patient and out-patient facilities of St. Petersburg from 2016 to 2019. Treatment outcomes were analyzed by subgroups formed taking into account resistance patterns and addition of bedaquiline to the treatment regimens: Ia – n = 94 (MDR TB; Bq-) and IIa ‒ n = 80 (XDR TB; Bq-); Ib ‒ n = 22 (MDR TB; Bq+) and IIb ‒ n = 23 (XDR TB; Bq+). Clinical and laboratory parameters of patients, the severity of comorbidity were assessed before the start of treatment, after 3, 6, 12-14 and 18-24 months of therapy, as well as after therapy completion and during the follow-up period. Statistical analysis was carried out using Statistica 10.0 and methods of parametric and nonparametric statistics and the SPSS 16.0 software, where p ≤ 0.05 was considered significant.Results. XDR TB patients in Subgroup IIb were significantly more likely to have a high level of comorbidity according to Charlson index (from 5 to 6 points) – in 34.7% of cases versus 5.0% in Subgroup IIa. At all stages of treatment in MDR TB patients with Bq+ (Ib), sputum conversion was recorded significantly more often versus patients of Subgroup Ia with Bq- when examined at all stages, with maximum effectiveness achieved by 18-24 months of treatment (90.9%). Treatment efficacy of XDR TB patients (IIb, Bq+) was also significantly higher versus treatment regimen containing no bedaquiline (60.8% (IIb, Bq+) versus 25.0% (IIa, Bq-), χ2 = 4.61, p < 0.05).Conclusions. Achieved high efficacy of therapy in Subgroups Ib and IIb containing Bq provided a positive impact on treatment default rates, that were recorded in a low percentage of cases in those subgroups. An ineffective course of treatment in MDR TB patients treated with regimens containing no Bq was observed in 42.5% in Subgroup Ia, while this rate made only 0.09% in Subgroup Ib. Treatment effectiveness was the highest in XDR TB patients of Subgroup IIb when Bq was added to the treatment regimen.

A Key Role of CD8+ T Cells in Controlling of Tuberculosis Infection

“…It is known that the presence of concomitant pathology, immunosuppression, HIV infection, malnutrition, and diabetes mellitus are the main risk factors for the development of tuberculosis infection [ 2 , 8 , 9 ]. The emergence of COVID-19 has led to adjustments being made, as it may be one of the factors influencing the development of active tuberculosis due to changes in immune status against the background of infection with the SARS-CoV-2 virus [ 10 ].…”

Tuberculosis in the Russian Federation: Dynamics of the Epidemic Indicators before and after COVID-19 Pandemic

“…In recent years, with the support of the government, new molecular genetic methods for diagnosing M. tuberculosis deoxyribonucleic acid (DNA) [ 24 ], as well as bacteriological methods (BACTEC MGIT), have been introduced in the Russian Federation. Additionally, new protocols have been developed for the treatment of drug-resistant tuberculosis with the use of bedaquiline [ 25 ], linezolid, and thioureidoiminomethylpyridinium perchlorate, all of which have been approved for use [ 26 , 27 ]. New methods of immunodiagnostics have been introduced (such as testing with a recombinant tuberculosis allergen (Diaskintest ® )), ELISPOT, QuantiFERON-TB Gold) [ 28 , 29 ], and computed tomography has been introduced into the diagnostic protocol.…”