Study of drug susceptibility of Mycobacterium tuberculosis to delamanid using BACTECTM MGITTM 960 automated system

Aim. To study the susceptibility of clinical strains of M. tuberculosis complex (MTB) to delamanid using the automated Bactec MGIT system. Material and methods. We studied 79 M. tuberculosis isolates from 78 TB patients treated in 2017-2023. 39 MTB strains were susceptibile and 40 had different drug resistance profiles to anti-tubercular drugs. Minimum inhibitory concentrations (MIC) of delamanid in Middlebrook 7H9 liquid medium were determined using the Bactec MGIT system, the susceptibility results were assessed using the critical concentration of 0.06 μg/ml recommended by WHO. Whole genome sequencing was used to identify mutations associated with phenotypic resistance to delamanid in MTB strains. Results. Delamanid demonstrated high activity against drug-naive MTB strains. MIC values ranged from 0.004 to 0.03 μg/ml for 97.4% (76/78) of studied susceptible MTB strains. Two MTB strains isolated from newly diagnosed patients with pulmonary TB had primary resistance to delamanid (2.6%; 2/78), and acquired resistance was detected in one MTB strain (2.6%; 1/39) during delamanid-based therapy for drugresistant TB. Genetic determinants of resistance were detected in three clinical MTB strains (N91T and W88* mutations in the ddn gene and Q299* mutation in the fgd1 gene) with MICs exceeding the critical concentration.