Zhang Ruixian, Luo Sha, Wang Nan, Zhang Hongying, Wu Xuping
The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210003, People's Republic of China.
Nanjing Center for Disease Control and Prevention Affiliated to Nanjing Medical University, Nanjing, Jiangsu, 210008, People's Republic of China.
Infect Drug Resist. 2023 May 6;16:2751-2764. doi: 10.2147/IDR.S408986. eCollection 2023.
Nontuberculous mycobacteria (NTM) are easily misdiagnosed as multidrug-resistant tuberculosis (MDR-TB), and treatment drugs are very limited. The main objective of our study was to evaluate the minimal inhibitory concentration (MIC) in vitro of bedaquiline (BDQ), clofazimine (CFZ), linezolid (LZD), delamanid (DLM), and pretomanid (PA-824) for treatment of and . Furthermore, we determined whether , and were related to drug resistance to provide an experimental basis for the use of these five drugs in the treatment of NTM.
We identified sample characteristics of epidemics in 550 patients with suspected NTM infection in Nanjing from 2019 to 2021 using the PCR-reverse spot hybrid method. Furthermore, we evaluated the MIC of BDQ, CFZ, DLM, LZD, and PA-824 against 155 clinical isolates of NTM using the microbroth dilution method. The resistant isolates were sequenced using Sanger sequencing.
The top three dominant species of NTM distributed in Nanjing were , and . Notably, the proportion of infections increased. The proportion of increased from 12% in 2019 to 18% in 2021. Demographic analysis showed that female infection rates were substantialy greater than male for (P=0.017, <0.05). Our results demonstrate that NTM are highly sensitive to bedaquiline and clofazimine in vitro. However, delamanid and pretomanid had little effect on and . In addition, we found 30-41 nucleotide deletion mutations and some novel point mutations in the gene of that are resistant to clofazimine.
Bedaquiline, clofazimine, and linezolid were more successful in vitro treatments against and . The mutation may be associated with resistance of to clofazimine.
非结核分枝杆菌（NTM）易被误诊为耐多药结核病（MDR-TB），且治疗药物非常有限。我们研究的主要目的是评估贝达喹啉（BDQ）、氯法齐明（CFZ）、利奈唑胺（LZD）、德拉马尼（DLM）和普瑞马尼德（PA-824）对[具体菌株1]和[具体菌株2]的体外最低抑菌浓度（MIC）。此外，我们确定了[具体基因1]、[具体基因2]和[具体基因3]是否与耐药性相关，为这五种药物用于NTM治疗提供实验依据。
我们采用PCR-反向斑点杂交法确定了2019年至2021年南京550例疑似NTM感染患者的疫情样本特征。此外，我们使用微量肉汤稀释法评估了BDQ、CFZ、DLM、LZD和PA-824对155株NTM临床分离株的MIC。对耐药分离株进行桑格测序。
南京分布的NTM前三位优势菌种为[具体菌种1]、[具体菌种2]和[具体菌种3]。值得注意的是，[具体菌种1]感染的比例有所增加。[具体菌种1]的比例从2019年的12%增加到2021年的18%。人口统计学分析表明，[具体菌种1]女性感染率显著高于男性（P=0.017，<0.05）。我们的结果表明，NTM在体外对贝达喹啉和氯法齐明高度敏感。然而，德拉马尼和普瑞马尼德对[具体菌株1]和[具体菌株2]几乎没有作用。此外，我们在[具体菌种1]对氯法齐明耐药的[具体基因1]中发现了30-41个核苷酸缺失突变和一些新的点突变。
贝达喹啉、氯法齐明和利奈唑胺在体外对[具体菌株1]和[具体菌株2]的治疗更成功。[具体基因1]突变可能与[具体菌种1]对氯法齐明的耐药性有关。
