Population-level emergence of bedaquiline and clofazimine resistance-associated variants among patients with drug-resistant tuberculosis in southern Africa: a phenotypic and phylogenetic analysis.

The Lancet. Microbe, Volume: 1, Issue: 4
August 1, 2020
Camus Nimmo C, James Millard J, Lucy van Dorp L, Kayleen Brien K, Sashen Moodley S, Allison Wolf A, Alison D Grant AD, Nesri Padayatchi N, Alexander S Pym AS, Fran├žois Balloux F, Max O'Donnell M

Bedaquiline and clofazimine are important drugs in the treatment of drug-resistant tuberculosis and are commonly used across southern Africa, although drug susceptibility testing is not routinely performed. In this study, we did a genotypic and phenotypic analysis of drug-resistant isolates from cohort studies in hospitals in KwaZulu-Natal, South Africa, to identify resistance-associated variants (RAVs) and assess the extent of clofazimine and bedaquiline cross-resistance. We also used a comprehensive dataset of whole-genome sequences to investigate the phylogenetic and geographical distribution of bedaquiline and clofazimine RAVs in southern Africa.