In vitro drug susceptibility of bedaquiline, delamanid, linezolid, clofazimine, moxifloxacin, and gatifloxacin against extensively drug -resistant tuberculosis from Beijing, China [PublishAheadOfPrint]

Extensively drug-resistant tuberculosis (XDR-TB) is a deadly form of TB that can be incurable due to its extreme drug resistance. In this study, we aimed to explore in vitro drug susceptibility of bedaquiline (BDQ), delamanid (DMD), linezolid (LZD), clofazimine (CLO), moxifloxacin (MXF), and gatifloxacin (GAT) against 90 XDR-TB strains isolated from patients in China. We also described the genetic characteristics of XDR-TB isolates with acquired drug resistance. Resistance to MFX, GAT, LZD, CLO, DMD and BDQ was found in 82 (91.1%), 76 (84.4%), 5 (5.6%), 5 (5.6%), 4 (4.4%) and 3 (3.3%) isolates among the XDR-TB strains, respectively. The most frequent mutations conferring fluoroquinolone resistance occurred in codon 94 of gyrA gene (57.8%), and the strains with these mutations (69.2%) were associated with high-level MFX-resistance compared to strains with mutations in codon 90 (25.0%, P<0.01). All the 5 CLO-resistant isolates exhibited >=4-fold upward shifts in BDQ minimal inhibitory concentration, which were attributed to mutations of codons 53 (60.0%) and 157 (20.0%) in Rv0678 gene. Additionally, mutation in codon 318 of fbiC gene was identified as the sole mutation related to DMD resistance. In conclusion, our data demonstrate that the XDR-TB strains exhibit strikingly high proportion of resistance to the current anti-TB drugs, whereas BDQ, DMD, LZD and CLO exhibit excellent in vitro activity against XDR-TB in a National TB Center of China. The extensive cross-resistance between OFX and later-generation fluoroquinolones indicates that MFX and GAT may have difficulty in producing the desired effect for XDR-TB patients under current settings.

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