J Glob Antimicrob Resist. 2021 Jun 29:S2213-7165(21)00160-0. doi: 10.1016/j.jgar.2021.06.007. Online ahead of print.
OBJECTIVES: New anti-TB drugs delamanid and bedaquiline appear as the last line to defense drug-resistant tuberculosis. Understanding the background prevalence of resistance to new drugs can help predict the lifetime of these drugs' effectiveness and inform regimen design.
METHODS: TB strains without prior exposure to novel anti-TB drugs were analyzed retrospectively. Drug susceptibility testing was conducted for TB strains with bedaquiline, delamanid, linezolid, clofazimine, and widely-used first- and second-line anti-TB drugs. All TB isolates with resistance to new or repurposed drugs were subjected to whole-genome sequencing to explore molecular characteristics of resistance and perform the phylogenetic analysis.
RESULTS: Overall, resistance to delamanid, bedaquiline, linezolid and clofazimine were observed in 0.7% (11/1603), 0.4% (6/1603), 0.4% (7/1603) and 0.4% (6/1603) of strains, respectively. Moreover, 1.0% (1/102) and 2.9% (3/102), 3.9% (4/102) and 1.0% (1/102) of MDR-TB strains were resistant to bedaquiline, delamanid, linezolid and clofazimine, respectively. Whereas 22.22% (2/9) of XDR-TB strains were resistant to both delamanid and linezolid, and none was resistant to bedaquiline or clofazimine. Phylogenetic analysis showed that recent transmission occurred in two XDR-TB strains with additional resistance to delamanid and linezolid. None known gene mutation associated with delamanid resistance was detected. All four strains with cross-resistance between bedaquiline and clofazimine were identified with a related gene mutation in Rv0678. Three out of five strains with linezolid resistance were detected gene mutation in rplC.
CONCLUSIONS: The detection of resistance to new anti-TB drugs emphasizes the pressing need for intensive surveillance for such resistance before wide-usage.