Clinical effectiveness of bedaquilin and delamanid treatment of children and adolescents with drug-­resistant tuberculosis

Objective — to study the clinical effectiveness of chemotherapy using bedaquiline (Bdq) and delamanid (Dlm) in children and adolescents with multidrug-resistant (MDR) and extensive drug resistant (XDR) pulmonary tuberculosis of lungs (TBL). 
Materials and methods. A retrospective cohort analysis of the medical records of 40 patients with pulmonary tuberculosis (TB) with MDR/XDR was conducted in order to study the clinical effectiveness of chemotherapy with Bdq and Dlm. Among 40 patients were 25 (62.5 %) children aged 0 to 14 years and 15 (37.5 %) — teenagers aged 15 to 17; there were 18 (47.5 %) boys, 22 (52.5 %) girls. The patients were divided into two groups: the first group — 25 children and the second group — 15 teenagers. Microbiological research in children and adolescents included: detection of Mycobacterium tuberculosis (MTB) in sputum by smear microscopy, sowing of material on Levenstein—Jensen medium, typing of isolated mycobacteria on BACTEC MGIT 960, determination of the drug susceptibility test of strains of MTB to antituberculosis drugs (ATBDs) of first- and second-line, as well as molecular genetic research of sputum, in particular by GeneXpert MTB/RIF/Ultra and linear probe analysis. All children and adolescents received an individualized treatment regimen depending on the resistance of MTB to ATBDs or on the resistance of MTB at the source of infection. 
Results and discussion. Among the examined children (25), who were prescribed Bdq and Dlm, almost half (44.0 %) were aged from 0 to 4 years, 12.0 % — from 5 to 8 years and 44.0 % — from 9 to 14 years. Patients aged 17 years (46.7 %) prevailed among teenagers (15). MDR/RIF-TB was diagnosed in 10 (40.0%), XDR-TB determined in 3 (12.0 %) and risk of MDR-TB (RMDR-TB) — in 12 (48.0 %) children who were prescribed a new treatment regimen with Bdq and Dlm. At the same time, MDR-TB diagnosed 1.7 times more often, XDR-TB 2.8 times more often and RMDR-TB 3.3 times less often among adolescents compared to children.The primary tuberculous complex found in 12 (48.0 %) children, TB damage of lung and bone — in 4 (16.0 %), TB of the intrathoracic lymph nodes — in 3 (12.0 %), TB of the lungs and central nervous system — in 2 (8.0 %) and infiltrative TB of the lungs — in 3 (12.0 %). The infiltrative pulmonary TB was observed 7.5 times more often and the disseminated form 3.3 times more often in adolescents than in children.All children didn’t excretion of MTB after the two months of treatment with Bdq and Dlm. However, non-bacterial excretion in all adolescents was achieved within 3 months of chemotherapy (CT). Significant positive X-ray dynamics were found in 23 (92.0 %) children and 12 (80.0 %) adolescents during 9 months of CT. Lung changes remained in 2 (8.0 %) children and 3 (20.0 %) adolescents after 9 months of treatment. However, in both children and adolescents resolution of infiltration, densification of focies and formation of fibrosis in the lungs were confirmed radiologically at the end of the course of treatment. 
Conclusions. Among 21 (84.0%) children and 10 (66.7 %) adolescents were cured at the end of the course of complex treatment with the use of Bdq and Dlm. Treatment was completed 2 times more often in adolescents than in children (33.3 vs. 16.0 %, p < 0.05). The success of the treatment at the occurrence of new ATBDs was established in all children and adolescents. In addition, among 84.0 % children and 73.3 % adolescents the treatment ended with the formation of small residual changes.