Variant Subpopulations in Nitroimidazole Resistance Genes in DELIBERATE trial participants
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Targeted next-generation sequencing (tNGS) enables rapid detection of drug resistance in Mycobacterium tuberculosis (Mtb), including minor variants that may indicate emerging resistance. We applied tNGS to isolates from 34 (of 49 eligible) participants in a randomized trial of bedaquiline (BDQ) and delamanid (DLM) co-administration for multidrug-resistant TB (MDR-TB). We detected baseline nonsynonymous variants in the nitroimidazole resistance genes fgd2 and ddn (BDQ arm) and fbiB (DLM arm) among 2/12 and 2/12 patients, respectively, and emergent subpopulations with nonsynonymous variants in fbiB, fbiC, and ddn as early as week 1 in 3/34 patients. These findings demonstrate that variants in nitroimidazole resistance genes may be present in the absence of drug exposure, and that tNGS can effectively track variant emergence during MDR-TB treatment.
