A Case of Transmission of Bedaquiline- and Linezolid-Resistant Tuberculosis.

Tuberculosis is one of the hardest-to-treat bacterial diseases with a high capacity to develop antibiotic resistance. The treatment scheme based on bedaquiline and linezolid was introduced in Russia in 2014 and, since 2018, has been widely used for the treatment of resistant tuberculosis. In our study of clinical M. tuberculosis isolates, we identified a case of a recent transmission of a strain with mutations in the genes rv0678 and rplC, associated with resistance to bedaquiline and linezolid. We analyzed five isolates obtained from patient A between 2015 and 2019 after unsuccessful treatment and three isolates from patient B obtained between diagnosis in 2019 and death in mid-2020 via whole-genome sequencing and 24-loci MIRU-VNTR genotyping. During the treatment of patient A, a large spectrum of different mutations in rv0678 developed, accompanied by an increase in bedaquiline MIC from 0.06 to 0.5 mg/L. Simultaneously, rplC C154R substitution emerged, leading to linezolid resistance. The isolates from patient B contained nearly the same mutation spectra as the isolates from patient A, differing in only four variants that emerged during transmission. The possible transmission event must have occurred in a public place in Moscow, since there was no evidence of direct contact between the patients. This finding confirms the worrying trend of untreatable M. tuberculosis strains circulating in the general population.