National Tuberculosis Clinical Laboratory, Beijing Key laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beiguan St #9, Beijing 101149, China.
National Tuberculosis Clinical Laboratory, Beijing Key laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beiguan St #9, Beijing 101149, China.
J Infect. 2021 Mar;82(3):371-377. doi: 10.1016/j.jinf.2021.02.004. Epub 2021 Feb 5.
The drug resistance prevalence data facilitates selection of the initial drug for treating multidrug-resistant tuberculosis (MDR-TB). The aim of this study was to investigate the prevalence and molecular characterization of seven additional types of drug resistances among MDR-TB isolates collected from the first/only nationwide drug resistance surveillance in China. A total of 391 out of the 401 MDR-TB strains were successfully recovered by Löwenstein-Jensen medium. Drug susceptibility testing was performed against moxifloxacin (Mfx), bedaquiline (Bdq), linezolid (Lzd), clofazimine (Cfz), cycloserine (Cs), delamanid (Dlm) and pyrazinamide (PZA). The strains were subjected to whole-genome sequencing for the analysis corresponding drug resistant genes and their profiles. 269 (68.80%) were simple MDR-TB, 28 (7.16%) were extensively drug-resistant tuberculosis (XDR-TB) and 94 (24.04%) were pre-XDR-TB. Dlm, Lzd, Cfz and Bdq presented the lowest drug resistant rates i.e. 3.32% (13/391), 3.84% (15/391),6.65% (26/391) and 7.16% (28/391), respectively. Mfx (17.39%, 68/391) and CS (13.55%, 53/391) also demonstrated strong potencies against the MDR strains, whereas PZA (38.36%, 150/391) presented much higher resistant rate. 54.41% (37/68) Mfx-resistant strains carried mutations located within gyrA or gyrB. 70.15% (94/134) PZA-resistant strains had pncA mutations. Two of the 26 Cfz-resistant isolates had mutation in Rv0678 were also resistant to Bdq. Dlm, Lzd, Cfz and Bdq exhibited excellent activity against MDR-TB, including XDR-TB. These data highlighted the necessity of a timely, feasible and reliable DST, while genotypic DST for Mfx and PZA is promising at this moment.
耐药流行数据有助于选择治疗耐多药结核病（MDR-TB）的初始药物。本研究旨在调查从中国首次/唯一全国耐药监测中收集的 MDR-TB 分离株中七种额外耐药类型的流行情况和分子特征。总共从 401 株 MDR-TB 菌株中成功恢复了 391 株，采用 Löwenstein-Jensen 培养基进行。对莫西沙星（Mfx）、贝达喹啉（Bdq）、利奈唑胺（Lzd）、氯法齐明（Cfz）、环丝氨酸（Cs）、德拉马尼（Dlm）和吡嗪酰胺（PZA）进行了药敏试验。对菌株进行全基因组测序，分析相应的耐药基因及其谱。269 株（68.80%）为单纯 MDR-TB，28 株（7.16%）为广泛耐药结核病（XDR-TB），94 株（24.04%）为前广泛耐药结核病。Dlm、Lzd、Cfz 和 Bdq 的耐药率最低，分别为 3.32%（13/391）、3.84%（15/391）、6.65%（26/391）和 7.16%（28/391）。Mfx（17.39%，68/391）和 CS（13.55%，53/391）对 MDR 株也具有很强的活性，而 PZA（38.36%，150/391）的耐药率则较高。54.41%（37/68）Mfx 耐药株携带位于 gyrA 或 gyrB 内的突变。70.15%（94/134）PZA 耐药株有 pncA 突变。26 株 Cfz 耐药株中有 2 株在 Rv0678 发生突变，也对 Bdq 耐药。Dlm、Lzd、Cfz 和 Bdq 对 MDR-TB，包括 XDR-TB，均表现出良好的活性。这些数据强调了及时、可行和可靠的药物敏感性检测的必要性，而目前 Mfx 和 PZA 的基因型药物敏感性检测很有前景。
