Abstract
Background: Linezolid, bedaquiline, and newer fluoroquinolones are currently placed as priority Group A drugs for the treatment of drug-resistant tuberculosis. The number of reported linezolid-resistant clinical strains is still low, and the correlation of molecular determinants with phenotype is not perfect. Methods: We determined the linezolid MICs for clinical isolates from the Moscow region and identified mutations in rplC and rrl genes. Results: All 16 linezolid-resistant isolates had previously reported mutations in the rplC or rrl loci, and 13 of them bore a RplC C154R substitution. Detection of this substitution in a heteroresistant state was not successful, probably, due to the more stable DNA secondary structure of the mutated fragment, which precludes its amplification in mixes with the wild-type DNA. Strains with an rplC mutation had higher linezolid MIC compared to isolates with rrl mutations. Conclusions: Linezolid resistance mostly emerged during treatment with the latest regimen. Three primary cases with linezolid resistance question the possible transmission of totally drug-resistant tuberculosis in the Moscow region, which demands further investigation.
Highlights
Multidrug-resistant (MDR) tuberculosis is a global public health threat, and three countries—India, China, and Russia—account for almost half of all cases [1]
Phenotypic linezolid resistance determination has been systematically performed at Moscow Research and Clinical Center for Tuberculosis Control protocols since December 2016
Cultures from 322 patients, who were scheduled to be treated with a bedaquiline- and linezolid-containing regimen, were analyzed
Summary
Multidrug-resistant (MDR) tuberculosis is a global public health threat, and three countries—India, China, and Russia—account for almost half of all cases [1]. Bedaquiline, and the newer fluoroquinolones are currently placed as priority Group A drugs, endorsed by the WHO for resistant tuberculosis treatment [6]. Bedaquiline, and newer fluoroquinolones are currently placed as priority Group A drugs for the treatment of drug-resistant tuberculosis. Methods: We determined the linezolid MICs for clinical isolates from the Moscow region and identified mutations in rplC and rrl genes. Results: All 16 linezolid-resistant isolates had previously reported mutations in the rplC or rrl loci, and 13 of them bore a RplC C154R substitution. Detection of this substitution in a heteroresistant state was not successful, probably, due to the more stable DNA secondary structure of the mutated fragment, which precludes its amplification in mixes with the wild-type DNA. Three primary cases with linezolid resistance question the possible transmission of totally drug-resistant tuberculosis in the Moscow region, which demands further investigation
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