National Clinical Laboratory on Tuberculosis, Beijing Key laboratory for 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 for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China
Antimicrob Agents Chemother. 2018 Jun 26;62(7). doi: 10.1128/AAC.00072-18. Print 2018 Jul.
Due to the natural resistance of nontuberculous mycobacteria (NTM) to many antibiotics, the treatment of diseases caused by NTM is often long-term but unsuccessful. The main goal of this study was to evaluate the susceptibilities to clofazimine of 209 isolates consisting of different NTM species isolated in Beijing, China. Furthermore, 47 reference strains were also tested, including 30 rapidly growing mycobacterium (RGM) species and 17 slowly growing mycobacterium (SGM) species. The potential molecular mechanism contributing to clofazimine resistance of NTM was investigated as well. Clofazimine exhibited excellent activity against both reference strains and clinical isolates of different SGM species, and most of the strains had MICs far below 1 μg/ml. Although the majority of the clinical isolates of and had MICs higher than 2 μg/ml, 17 out of the 30 reference strains of different RGM species had MICs below 1 μg/ml According to the MIC distributions, the tentative epidemiological cutoff (ECOFF) values for , , and were defined at 0.5 μg/ml, 1 μg/ml, and 2 μg/ml, respectively. Intriguingly, single-direction cross-resistance between bedaquiline- and clofazimine (Cfz)-resistant isolates was observed among the tested NTM species. This study demonstrates that clofazimine had strong activity against most SGM species , as well as some RGM species. The data provide important insights into the possible clinical application of Cfz to treat NTM infections.
由于非结核分枝杆菌(NTM)对许多抗生素具有天然耐药性,因此治疗 NTM 引起的疾病往往需要长期治疗但效果不佳。本研究的主要目的是评估 209 株来自中国北京的不同 NTM 分离株对氯法齐明的敏感性。此外,还测试了 47 株参考菌株,包括 30 株快速生长分枝杆菌(RGM)和 17 株缓慢生长分枝杆菌(SGM)。还研究了导致 NTM 对氯法齐明耐药的潜在分子机制。氯法齐明对参考菌株和不同 SGM 种的临床分离株均表现出优异的活性,大多数菌株的 MIC 远低于 1μg/ml。尽管大多数 和 临床分离株的 MIC 高于 2μg/ml,但 30 株不同 RGM 种的参考菌株中有 17 株的 MIC 低于 1μg/ml。根据 MIC 分布,分别将 、 和 的暂定流行病学截断值(ECOFF)值定义为 0.5μg/ml、1μg/ml 和 2μg/ml。有趣的是,在测试的 NTM 种中,贝达喹啉和氯法齐明(Cfz)耐药分离株之间观察到单向交叉耐药性。本研究表明,氯法齐明对大多数 SGM 种以及一些 RGM 种具有很强的活性。这些数据为 Cfz 治疗 NTM 感染的可能临床应用提供了重要的见解。