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不同结核分枝杆菌谱系间结核耐药性与分子检测方法的比较研究

Comparative Study on Tuberculosis Drug Resistance and Molecular Detection Methods Among Different Mycobacterium Tuberculosis Lineages.

作者信息

He Chuan-Jiang, Wan Jiang-Li, Luo Sheng-Fang, Guo Rui-Jie, Paerhati Pawuziye, Cheng Xiang, Duan Chao-Hui, Xu Ai-Min

机构信息

Department of Laboratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China.

Department of Laboratory Medicine, The First People's Hospital of Kashgar, Kashgar, 844000, People's Republic of China.

出版信息

Infect Drug Resist. 2023 Sep 7;16:5941-5951. doi: 10.2147/IDR.S423390. eCollection 2023.

DOI:10.2147/IDR.S423390
PMID:37700800
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10494918/
Abstract

PURPOSE

This study aims to compare drug resistance and detection efficacy across different Mycobacterium tuberculosis lineages, offering insights for precise treatment and molecular diagnosis.

METHODS

161 strains of Mycobacterium tuberculosis ( were tested for drug resistance using Phenotypic Drug Susceptibility Testing (pDST), High-Resolution Melting analysis (HRM), and Whole Genome Sequencing (WGS) methods. The main focus was on evaluating the accuracy of different methods for detecting resistance to rifampicin (RIF), isoniazid (INH), and streptomycin (SM).

RESULTS

Among the 161 strains of , 83.85% (135/161) were fully sensitive to RIF, INH, and SM according to pDST, and the rate of multidrug resistance was 4.35% (7/161). The drug resistance rates of lineage 2 to the three drugs (26/219, 11.87%) were significantly higher than those of non-lineage 2 (12/264, 4.45%) (P<0.05). Compared with pDST, WGS had a sensitivity of 100%, 94.12%, and 92.31% and a specificity of 100%, 99.31%, and 98.65% for RIF, INH, and SM, respectively, with no significant difference. The sensitivity of HRM for RIF, INH, and SM was 87.50%, 52.94%, and 76.92%, respectively, while the specificity was 96.08%, 99.31%, and 99.32%, respectively. The sensitivity of HRM for detecting INH resistance was significantly lower than that of pDST (=0.039). Compared with HRM, WGS increased the sensitivity of RIF, INH, and SM by 12.50%, 41.18%, and 15.38%, respectively.

CONCLUSION

There are significant differences in drug resistance rates among different lineages of , with lineage 2 having higher rates of RIF, INH, and SM resistance than lineages 3 and 4. The sensitivity of HRM is far lower than that of pDST, and currently, the accuracy of HRM is not sufficient to replace pDST. WGS has no significant difference in detecting drug resistance compared with pDST but can identify new anti-tuberculosis drug-resistant mutations, providing effective guidance for clinical decision-making.

摘要

目的

本研究旨在比较不同结核分枝杆菌谱系的耐药性及检测效能,为精准治疗和分子诊断提供见解。

方法

采用表型药物敏感性试验(pDST)、高分辨率熔解分析(HRM)和全基因组测序(WGS)方法对161株结核分枝杆菌进行耐药性检测。主要重点是评估不同方法检测利福平(RIF)、异烟肼(INH)和链霉素(SM)耐药性的准确性。

结果

在161株菌株中,根据pDST,83.85%(135/161)对RIF、INH和SM完全敏感,多药耐药率为4.35%(7/161)。2型谱系对这三种药物的耐药率(26/219,11.87%)显著高于非2型谱系(12/264,4.45%)(P<0.05)。与pDST相比,WGS对RIF、INH和SM的敏感性分别为100%、94.12%和92.31%,特异性分别为100%、99.31%和98.65%,无显著差异。HRM对RIF、INH和SM的敏感性分别为87.50%、52.94%和76.92%,而特异性分别为96.08%、99.31%和99.32%。HRM检测INH耐药性的敏感性显著低于pDST(P=0.039)。与HRM相比,WGS对RIF、INH和SM的敏感性分别提高了12.50%、41.18%和15.38%。

结论

不同结核分枝杆菌谱系的耐药率存在显著差异,2型谱系对RIF、INH和SM的耐药率高于3型和4型谱系。HRM的敏感性远低于pDST,目前,HRM的准确性不足以替代pDST。与pDST相比,WGS在检测耐药性方面无显著差异,但可识别新的抗结核耐药突变,为临床决策提供有效指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d456/10494918/32175ffd3e9c/IDR-16-5941-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d456/10494918/5515fc0d4f84/IDR-16-5941-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d456/10494918/32175ffd3e9c/IDR-16-5941-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d456/10494918/5515fc0d4f84/IDR-16-5941-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d456/10494918/32175ffd3e9c/IDR-16-5941-g0002.jpg

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