In Vitro Drug Susceptibility of Bedaquiline, Delamanid, Linezolid, Clofazimine, Moxifloxacin, and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing, China
In Vitro Drug Susceptibility of Bedaquiline, Delamanid, Linezolid, Clofazimine, Moxifloxacin, and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing, China
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DOI：
10.1128/aac.00900-17
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发表时间：
2017-10-01
影响因子：
4.9
通讯作者：
Huang, Hairong
中科院分区：
文献类型：
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作者：
Pang, Yu;Zong, Zhaojing;Huang, Hairong
广泛耐药结核病(XDR-TB)是一种致命的结核病，由于其极端的耐药性，可能是无法治愈的。本研究旨在探讨中国地区90株广泛耐药结核分枝杆菌对贝达奎兰、地拉米德、利奈唑胺、氯法齐明、莫西沙星和加替沙星的体外敏感性。我们还描述了具有获得性耐药的广泛耐药结核分离株的遗传特征。耐MFX 82株(91.1%)，耐GAT 76株(84.4%)，耐CLO 5株(5.6%)，耐DMD 5株(5.6%)，耐DMD 4株(4.4%)，耐BDQ 3株(3.3%)。与氟喹诺酮类药物耐药相关的突变以gyrA基因第94位密码子突变最为常见(57.8%)，与90位密码子突变株(25.0%)相比，该突变株(69.2%)对甲氧西林高度耐药(P<；0.01)。所有5株耐CLO菌株的BDQ MIC均出现-gt；=4倍的上移，这归因于Rv0678基因53(60.0%)和157(20.0%)密码子的突变。此外，FbIC基因318位密码子突变是唯一与DMD抗性相关的突变。综上所述，我们的数据表明，广泛耐药结核病菌株对现有抗结核药物表现出惊人的高耐药率，而国家结核病临床研究中心中国的研究发现，BDQ、DMD、LZD和CLO对广泛耐药结核病表现出良好的体外活性。OFX和新一代氟喹诺酮类药物之间广泛的交叉耐药性表明，MFX和GAT可能难以为广泛耐药结核病患者产生预期的效果。
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 the in vitro susceptibility to bedaquiline (BDQ), delamanid (DMD), linezolid (LZD), clofazimine (CLO), moxifloxacin (MFX), and gatifloxacin (GAT) of 90 XDR-TB strains isolated from patients in China. We also describe 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 the gyrA gene (57.8%), and the strains with these mutations (69.2%) were associated with highlevel MFX resistance compared to strains with mutations in codon 90 (25.0%) (P < 0.01). All 5 CLO-resistant isolates exhibited >= 4-fold upward shifts in the BDQ MIC, which were attributed to mutations of codons 53 (60.0%) and 157 (20.0%) in the Rv0678 gene. Additionally, mutation in codon 318 of the fbiC gene was identified as the sole mutation related to DMD resistance. In conclusion, our data demonstrate that the XDR-TB strains exhibit a 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 the National Clinical Center on TB 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.