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  • Title: Prevalence of Mycobacterium tuberculosis resistant to bedaquiline and delamanid in China.
    Author: He W, Liu C, Liu D, Ma A, Song Y, He P, Bao J, Li Y, Zhao B, Fan J, Cheng Q, Zhao Y.
    Journal: J Glob Antimicrob Resist; 2021 Sep; 26():241-248. PubMed ID: 34214699.
    Abstract:
    OBJECTIVES: The new antituberculous drugs delamanid and bedaquiline form the last line of defence against drug-resistant tuberculosis (TB). Understanding the background prevalence of resistance to new drugs can help predict the lifetime of these drugs' effectiveness and inform regimen design. METHODS: Mycobacterium tuberculosis without prior exposure to novel anti-TB drugs were analysed retrospectively. Drug susceptibility testing for bedaquiline, delamanid, linezolid, clofazimine and widely used first- and second-line anti-TB drugs was performed. All TB isolates with resistance to new or repurposed drugs were subjected to whole-genome sequencing to explore the molecular characteristics of resistance and to perform phylogenetic analysis. RESULTS: Overall, resistance to delamanid, bedaquiline, linezolid and clofazimine was observed in 0.7% (11/1603), 0.4% (6/1603), 0.4% (7/1603) and 0.4% (6/1603) of TB isolates, respectively. Moreover, 1.0% (1/102), 2.9% (3/102), 3.9% (4/102) and 1.0% (1/102) of multidrug-resistant TB (MDR-TB) were resistant to bedaquiline, delamanid, linezolid and clofazimine, respectively. Whereas 22.2% (2/9) of extensively-drug resistant tuberculosis (XDR-TB) isolates 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 with additional resistance to delamanid and linezolid. None known gene mutation associated with delamanid resistance was detected. All four isolates with cross-resistance to bedaquiline and clofazimine had a detected gene mutation in Rv0678. Three of five strains with linezolid resistance had a detected gene mutation in rplC. CONCLUSION: Detection of resistance to new anti-TB drugs emphasises the pressing need for intensive surveillance for such resistance before their wide usage.
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