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评价全基因组序列预测中国宁波临床耐利福平分离株对九种抗结核药物的耐药性及耐药基因特征。

Evaluation of whole-genome sequence to predict drug resistance of nine anti- drugs and characterize resistance genes in clinical rifampicin-resistant isolates from Ningbo, China.

机构信息

Institute of Tuberculosis Prevention and Control, Ningbo Municipal Center for Disease Control and Prevention, Ningbo, China.

Center for Health Economics, Faculty of Humanities and Social Sciences, University of Nottingham, Ningbo, China.

出版信息

Front Public Health. 2022 Aug 18;10:956171. doi: 10.3389/fpubh.2022.956171. eCollection 2022.

Abstract

SETTING

Controlling drug-resistant in Ningbo, China.

OBJECTIVE

Whole-genome sequencing (WGS) has not been employed to comprehensively study isolates, especially rifampicin-resistant , in Ningbo, China. Here, we aim to characterize genes involved in drug resistance in RR-TB and create a prognostic tool for successfully predicting drug resistance in patients with TB.

DESIGN

Drug resistance was predicted by WGS in a "TB-Profiler" web service after phenotypic drug susceptibility tests (DSTs) against nine anti-TB drugs among 59 clinical isolates. A comparison of consistency, sensitivity, specificity, and positive and negative predictive values between WGS and DST were carried out for each drug.

RESULTS

The sensitivities and specificities for WGS were 95.92 and 90% for isoniazid (INH), 100 and 64.1% for ethambutol (EMB), 97.37 and 100% for streptomycin (SM), 75 and 100% for amikacin (AM), 80 and 96.3%for capreomycin (CAP), 100 and 97.22% for levofloxacin (LFX), 93.33 and 90.91% for prothionamide (PTO), and 70 and 97.96% for para-aminosalicylic acid (PAS). Around 53 (89.83%) and 6 (10.17%) of the isolates belonged to lineage two (East-Asian) and lineage four (Euro-American), respectively.

CONCLUSION

Whole-genome sequencing is a reliable method for predicting resistance to INH, RIF, EMB, SM, AM, CAP, LFX, PTO, and PAS with high consistency, sensitivity, and specificity. There was no transmission that occurred among the patients with RR-TB in Ningbo, China.

摘要

背景

在中国宁波控制耐多药结核病。

目的

全基因组测序(WGS)尚未用于全面研究中国宁波的 分离株,尤其是耐利福平的 。在这里,我们旨在研究 RR-TB 中与药物耐药相关的基因,并创建一种用于成功预测结核病患者药物耐药的预后工具。

设计

对 59 株临床分离株进行了针对 9 种抗结核药物的表型药敏试验(DST)后,在“TB-Profiler”网络服务中通过 WGS 预测药物耐药性。对每种药物进行了 WGS 与 DST 之间的一致性、敏感性、特异性以及阳性和阴性预测值的比较。

结果

WGS 的敏感性和特异性分别为异烟肼(INH)95.92%和 90%、乙胺丁醇(EMB)100%和 64.1%、链霉素(SM)97.37%和 100%、阿米卡星(AM)75%和 100%、卷曲霉素(CAP)80%和 96.3%、左氧氟沙星(LFX)100%和 97.22%、丙硫异烟胺(PTO)100%和 97.22%、对氨基水杨酸(PAS)70%和 97.96%。大约 53 株(89.83%)和 6 株(10.17%)分离株分别属于谱系 2(东亚)和谱系 4(欧洲-美洲)。

结论

WGS 是一种可靠的方法,可用于预测 INH、RIF、EMB、SM、AM、CAP、LFX、PTO 和 PAS 的耐药性,具有高一致性、敏感性和特异性。在中国宁波,耐多药结核病患者之间没有发生传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d8/9433565/fd5a278d9ba5/fpubh-10-956171-g0001.jpg

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