PDF(Pubmed)
Abstract：
UNASSIGNED: The surge of multidrug-resistant TB (MDR-TB) in Iran poses a significant challenge to global healthcare. The introduction of delamanid (DLM) and bedaquiline (BDQ), two potent antimycobacterial drugs, marks a crucial advance. Nevertheless, as resistance in Mycobacterium tuberculosis is on the rise in Iran and resistance to these newer medications is emerging, investigations in this field are of utmost importance.
UNASSIGNED: In this cross-sectional study, 38 MDR-TB strains were collected from five distinct regional TB laboratories in Iran. The clinical isolates were confirmed as M. tuberculosis using the phenotypic tests and IS6110-based PCR assay. Drug susceptibility testing (DST) for isoniazid, rifampicin, ethambutol, DLM, and BDQ was performed using WHO-approved methods. Sequencing was used to investigate genetic mutations in DLM (ddn, fgd1) and BDQ (Rv0678, atpE, pepQ) genes associated with resistance.
UNASSIGNED: Among the 38 collected MDR-TB isolates, 7 (18.5 %) exhibited resistance to DLM, while all remained susceptible to BDQ. Analysis of the sequencing data revealed that the ddn gene exhibited the highest number of mutations in DLM-resistant isolates, including 18 nonsynonymous mutations and 1 indel leading to frameshift mutations. A common mutation, Gly81Ser, was present in 4 of the DLM-resistant isolates (4/7; 57.1 %). A synonymous mutation, T960C, in the fgd1 gene was uniformly found in DLM-resistant samples. Notably, no significant mutations were observed in the atpE, Rv0678, or pepQ genes in any of the BDQ-susceptible isolates.
UNASSIGNED: Our study underscores the emergence of DLM resistance in a subset of MDR-TB isolates in Iran, primarily associated with mutations in the ddn gene. This emphasizes the ongoing necessity for TB drug resistance surveillance and research. While BDQ remains efficacious, the emergence of DLM resistance is a concerning development, warranting further exploration into resistance mechanisms and the formulation of effective TB control strategies.
UNASSIGNED: In this cross-sectional study, 38 MDR-TB strains were collected from five distinct regional TB laboratories in Iran. The clinical isolates were confirmed as M. tuberculosis using the phenotypic tests and IS6110-based PCR assay. Drug susceptibility testing (DST) for isoniazid, rifampicin, ethambutol, DLM, and BDQ was performed using WHO-approved methods. Sequencing was used to investigate genetic mutations in DLM (ddn, fgd1) and BDQ (Rv0678, atpE, pepQ) genes associated with resistance.
UNASSIGNED: Among the 38 collected MDR-TB isolates, 7 (18.5 %) exhibited resistance to DLM, while all remained susceptible to BDQ. Analysis of the sequencing data revealed that the ddn gene exhibited the highest number of mutations in DLM-resistant isolates, including 18 nonsynonymous mutations and 1 indel leading to frameshift mutations. A common mutation, Gly81Ser, was present in 4 of the DLM-resistant isolates (4/7; 57.1 %). A synonymous mutation, T960C, in the fgd1 gene was uniformly found in DLM-resistant samples. Notably, no significant mutations were observed in the atpE, Rv0678, or pepQ genes in any of the BDQ-susceptible isolates.
UNASSIGNED: Our study underscores the emergence of DLM resistance in a subset of MDR-TB isolates in Iran, primarily associated with mutations in the ddn gene. This emphasizes the ongoing necessity for TB drug resistance surveillance and research. While BDQ remains efficacious, the emergence of DLM resistance is a concerning development, warranting further exploration into resistance mechanisms and the formulation of effective TB control strategies.
摘要：
■伊朗的耐多药结核病（MDR-TB）激增，对全球医疗保健构成了重大挑战。德拉马尼德（DLM）和贝达奎林（BDQ）的引入，两种有效的抗分枝杆菌药物，标志着一个关键的进步。然而，由于伊朗结核分枝杆菌的耐药性正在上升，并且对这些新型药物的耐药性正在出现，这方面的调查至关重要。
■在这项横断面研究中，从伊朗五个不同的地区结核病实验室收集了38株耐多药结核病菌株。使用表型测试和基于IS6110的PCR测定将临床分离株确认为结核分枝杆菌。异烟肼的药敏试验(DST),利福平,乙胺丁醇,DLM,和BDQ使用WHO批准的方法进行。测序用于研究DLM的基因突变(ddn，fgd1）和BDQ（Rv0678，atpE，pepQ）与抗性相关的基因。
■在收集的38株耐多药结核病分离株中，7（18.5%）表现出对DLM的抗性，而所有人仍然容易受到BDQ的影响。对测序数据的分析表明，ddn基因在DLM抗性分离株中表现出最高数量的突变，包括18个非同义突变和1个导致移码突变的indel。一个常见的突变,Gly81Ser,存在于4株DLM抗性分离株中(4/7；57.1%)。同义突变,T960C,在DLM抗性样品中均匀地发现了fgd1基因。值得注意的是,在atpE中未观察到明显的突变，Rv0678或任何BDQ敏感分离株中的pepQ基因。
■我们的研究强调了在伊朗的一部分耐多药结核病分离株中出现了DLM耐药性，主要与ddn基因突变有关.这强调了结核病耐药性监测和研究的持续必要性。虽然BDQ仍然有效，DLM抗性的出现是一个令人担忧的发展，有必要进一步探索耐药机制和制定有效的结核病控制策略。
■在这项横断面研究中，从伊朗五个不同的地区结核病实验室收集了38株耐多药结核病菌株。使用表型测试和基于IS6110的PCR测定将临床分离株确认为结核分枝杆菌。异烟肼的药敏试验(DST),利福平,乙胺丁醇,DLM,和BDQ使用WHO批准的方法进行。测序用于研究DLM的基因突变(ddn，fgd1）和BDQ（Rv0678，atpE，pepQ）与抗性相关的基因。
■在收集的38株耐多药结核病分离株中，7（18.5%）表现出对DLM的抗性，而所有人仍然容易受到BDQ的影响。对测序数据的分析表明，ddn基因在DLM抗性分离株中表现出最高数量的突变，包括18个非同义突变和1个导致移码突变的indel。一个常见的突变,Gly81Ser,存在于4株DLM抗性分离株中(4/7；57.1%)。同义突变,T960C,在DLM抗性样品中均匀地发现了fgd1基因。值得注意的是,在atpE中未观察到明显的突变，Rv0678或任何BDQ敏感分离株中的pepQ基因。
■我们的研究强调了在伊朗的一部分耐多药结核病分离株中出现了DLM耐药性，主要与ddn基因突变有关.这强调了结核病耐药性监测和研究的持续必要性。虽然BDQ仍然有效，DLM抗性的出现是一个令人担忧的发展，有必要进一步探索耐药机制和制定有效的结核病控制策略。
