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Introduction. Nontuberculous mycobacteria (NTM) are widespread in the environment and can cause various diseases in humans, especially immunocompromised patients. Hypothesis. Treatment of diseases caused by NTM is a complicated issue, mainly due to the resistance of the pathogen to most antimicrobial agents. Bedaquiline (Bdq) is now widely used for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). Aim. The main goal of our study was to evaluate the activity of Bdq against Mycobacterium avium complex (MAC), the most common species among NTM. Methodology. A total of 166 MAC cultures (124 Mycobacterium avium and 42 Mycobacterium intracellulare ) were studied. The minimum inhibitory concentrations (MICs) of Bdq for M. avium and M. intracellulare were obtained by twofold serial dilutions in the Middlebrook 7H9 medium. MIC ranges were determined and the MIC 50 , MIC 90 and ECOFF values were obtained. Results. The MICs in respect of M. avium ranged from 0.003 to 1.0 µg ml -1 ; those for M. intracellulare ranged from 0.003 to 0.5 µg ml -1 . The Bdq MIC 50 and MIC 90 values were found to be 0.015 and 0.12 µg ml -1 , respectively, for M. avium and 0.007 and 0.06 µg ml -1 , respectively, for M. intracellulare . The tentative ECOFF values for M. avium and M. intracellulare were 0.12 and 0.06 µg ml -1 The main bedaquiline susceptibility parameters for MAC strains isolated in the Moscow region were determined.Conclusion. The main bedaquiline susceptibility parameters for MAC strains isolated in the Moscow region were determined.

Objectives: To study the isolates with acquired resistance to bedaquiline and linezolid that were obtained from patients enrolled in a clinical study of a novel therapy regimen for drug-resistant TB in Moscow, Russia., Methods: Linezolid resistance was detected using MGIT 960 with a critical concentration of 1 mg/L. The MIC of bedaquiline was determined using the proportion method. To identify genetic determinants of resistance, sequencing of the mmpR ( Rv0678 ), atpE , atpC , pepQ , Rv1979c , rrl , rplC and rplD loci was performed., Results: A total of 85 isolates from 27 patients with acquired resistance to linezolid and reduced susceptibility to bedaquiline (MIC ≥0.06 mg/L) were tested. Most mutations associated with a high MIC of bedaquiline were found in the mmpR gene. We identified for the first time two patients whose clinical isolates had substitutions D28N and A63V in AtpE, which had previously been found only in in vitro -selected strains. Several patients had isolates with elevated MICs of bedaquiline prior to treatment; four of them also bore mutations in mmpR , indicating the presence of some hidden factors in bedaquiline resistance acquisition. The C154R substitution in ribosomal protein L3 was the most frequent in the linezolid-resistant strains. Mutations in the 23S rRNA gene (g2294a and g2814t) associated with linezolid resistance were also found in two isolates. Heteroresistance was identified in ∼40% of samples, which reflects the complex nature of resistance acquisition., Conclusions: The introduction of novel drugs into treatment must be accompanied by continuous phenotypic susceptibility testing and the analysis of genetic determinants of resistance., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)