Detection of I491F and V170F rpoB mutations associated with misdiagnosis of rifampicin resistance among patients with drug-susceptible tuberculosis treatment failure, Myanmar, 2022

IF 3.7 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance Pub Date : 2025-01-08 DOI:10.1016/j.jgar.2024.12.026

Phyu Win Ei , Mi Mi Htwe , Myat Htut Nyunt , Aye Su Mon , Zaw Myint , Wint Wint Nyunt , Su Mon Win , Sandar Aung , Wai Myat Thwe , Wah Wah Aung

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引用次数: 0

Abstract

Objective

Detecting rifampicin (RIF) resistance is crucial in selecting tuberculosis (TB) treatment. Recently, several studies reported that I491F and V170F rpoB mutations were found with a varying prevalence. This study aimed to find out RIF resistance missed by routine diagnostic assays using next generation genome sequencing tool.

Methods

Sputum specimens from first-line TB treatment failed patients attending Tuberculosis Centers in Yangon Region during 2022 were cultured in solid media. Phenotypic drug susceptibility testing was conducted using Mycobacterial Growth Indicator Tube method. Whole genome or Deeplex-targeted next-generation sequencing was performed using Illumina Miseq. Mutation analysis was done by PhyResSE and SAM-TB online platforms.

Results

A total of 32 culture-positive isolates with DNA qualified for genome sequencing were included in the study. Those were diagnosed as rifampicin-susceptible by routine GeneXpert and line probe assays. RIF resistance-conferring mutations were found in 17/32 (53.1%) Mycobacterium tuberculosis isolates; 14 (43.7%) had mutations outside the RIF resistance determining region (I491F and V170F), two (6.3%) were S450L, mutation within RIF resistance determining region, and one isolate (3.1%) with interim resistance mutations S428T and S441A.

Conclusion

This study highlighted the presence of rifampicin-resistant TB strains missed by current diagnostic strategies, and are circulating as treatment-failed patients. This demonstrates a gap in current World Health Organization-endorsed algorithms for capturing all multidrug-resistant-TB strains.

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药敏结核治疗失败患者中I491F和V170F rpoB突变与利福平耐药误诊的相关性研究，缅甸，2022。

检测利福平耐药性对于选择结核病治疗方法至关重要。最近，几项研究报道了I491F和V170F rpoB突变，以前被指定为利福平耐药的临界突变，被发现具有不同的患病率。在固体培养基中培养2022年期间在仰光地区结核病中心就诊的一线结核病治疗失败患者的痰标本。采用分枝杆菌生长指示管（MGIT）法进行表型药敏试验（pDST）。使用Illumina Miseq进行全基因组或Deeplex靶向下一代测序。突变分析由PhyResSE和SAM-TB在线平台完成。本研究共纳入32株培养阳性分离株，其DNA符合基因组测序要求。通过常规GeneXpert和线探针检测诊断为利福平敏感的患者。32株结核分枝杆菌中有17株（53.1%）存在利福平耐药突变；14株（43.7%）存在RRDR外突变（I491F和V170F）， 2株（6.3%）存在RRDR内突变（S450L）， 1株（3.1%）存在过渡性耐药突变S428T和S441A。这项研究强调了当前诊断策略所遗漏的利福平耐药结核菌株的存在，并作为治疗失败的患者传播。这表明世卫组织目前认可的用于捕获所有耐多药结核病菌株的算法存在差距。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of global antimicrobial resistance INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY

CiteScore

8.70

自引率

2.20%

发文量

285

审稿时长

34 weeks

期刊介绍： The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes. JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR). Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.