National Clinical Laboratory on Tuberculosis, Beijing Key laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China
National Clinical Laboratory on Tuberculosis, Beijing Key laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
Antimicrob Agents Chemother. 2017 Sep 22;61(10). doi: 10.1128/AAC.00900-17. Print 2017 Oct.
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 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 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%) ( < 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 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 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.
广泛耐药结核病（XDR-TB）是一种致命形式的结核病，由于其极强的耐药性，可能无法治愈。在这项研究中，我们旨在探索 90 株来自中国患者的 XDR-TB 分离株对贝达喹啉（BDQ）、德拉马尼（DMD）、利奈唑胺（LZD）、氯法齐明（CLO）、莫西沙星（MFX）和加替沙星（GAT）的敏感性，并描述获得性耐药性的 XDR-TB 分离株的遗传特征。在 XDR-TB 菌株中，分别发现对 MFX、GAT、LZD、CLO、DMD 和 BDQ 的耐药率为 82（91.1%）、76（84.4%）、5（5.6%）、5（5.6%）、4（4.4%）和 3（3.3%）。导致氟喹诺酮类耐药的最常见突变发生在 基因的 94 密码子（57.8%），与 90 密码子突变的菌株（69.2%）相比，这些突变菌株（25.0%）与高水平 MFX 耐药相关（<0.01）。所有 5 株 CLO 耐药株的 BDQ MIC 均有≥4 倍的升高，这归因于 Rv0678 基因 53（60.0%）和 157（20.0%）密码子的突变。此外，在 基因的 318 密码子中发现了突变，这是与 DMD 耐药相关的唯一突变。总之，我们的数据表明，XDR-TB 菌株对当前抗结核药物表现出极高的耐药比例，而在中国国家结核病临床中心，BDQ、DMD、LZD 和 CLO 对 XDR-TB 具有极好的活性。OFX 和新一代氟喹诺酮类药物之间的广泛交叉耐药性表明，MFX 和 GAT 可能难以对 XDR-TB 患者产生预期的效果。
