Park Sanghee, Jung Jihee, Kim Jiyeon, Han Sang Bong, Ryoo Sungweon
Clinical Research Center, Masan National Tuberculosis Hospital, Changwon-si 51755, Korea.
Department of Laboratory Medicine, Masan National Tuberculosis Hospital, Changwon-si 51755, Korea.
J Clin Med. 2022 Mar 30;11(7):1927. doi: 10.3390/jcm11071927.
Recently, as clofazimine (CFZ) showed a good therapeutic effect in treating multi-drug-resistant tuberculosis (MDR-TB), the anti-tuberculosis activity and resistance were re-focused. Here, we investigated the CFZ resistance and genetic mutations of drug-resistant Mycobacterium tuberculosis (DR-Mtb) isolates to improve the diagnosis and treatment of drug-resistant TB patients. The minimal inhibitory concentration (MIC) of CFZ was examined by resazurin microtiter assay (REMA) with two reference strains and 122 clinical isolates from Korea. The cause of CFZ resistance was investigated in relation to the therapeutic history of patients. Mutations of Rv0678, Rv1979c and pepQ of CFZ resistant isolates were analyzed by PCR and DNA sequencing. The rate of CFZ resistance with MIC > 1 mg/L was 4.1% in drug-resistant Mtb isolates. The cause of CFZ resistance was not related to treatment with CFZ or bedaquiline. A CFZ susceptibility test should be conducted regardless of dugs use history. The four novel mutation sites were identified in the Rv0678 and pepQ genes related to CFZ resistance in this study.
最近，由于氯法齐明（CFZ）在治疗耐多药结核病（MDR-TB）方面显示出良好的治疗效果，其抗结核活性和耐药性再次受到关注。在此，我们研究了耐多药结核分枝杆菌（DR-Mtb）分离株对CFZ的耐药性和基因突变情况，以改善耐药结核病患者的诊断和治疗。采用刃天青微量滴定法（REMA）检测了来自韩国的2株参考菌株和122株临床分离株对CFZ的最低抑菌浓度（MIC）。结合患者的治疗史研究了CFZ耐药的原因。通过PCR和DNA测序分析了CFZ耐药分离株的Rv0678、Rv1979c和pepQ基因突变情况。耐多药结核分枝杆菌分离株中MIC>1mg/L的CFZ耐药率为4.1%。CFZ耐药的原因与CFZ或贝达喹啉治疗无关。无论用药史如何，均应进行CFZ药敏试验。本研究在与CFZ耐药相关的Rv0678和pepQ基因中鉴定出4个新的突变位点。
