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2023年两个欧盟国家参考实验室中结核病耐药性筛查的基因分型与表型分型的相对定位

The Relative Positioning of Genotyping and Phenotyping for Tuberculosis Resistance Screening in Two EU National Reference Laboratories in 2023.

作者信息

Anthony Richard, Groenheit Ramona, Mansjö Mikael, de Zwaan Rina, Werngren Jim

机构信息

National Tuberculosis Reference Laboratory, Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), 3721BA Bilthoven, The Netherlands.

Supranational Reference Laboratory for Tuberculosis, Public Health Agency of Sweden, 171 82 Solna, Sweden.

出版信息

Microorganisms. 2023 Jul 14;11(7):1809. doi: 10.3390/microorganisms11071809.

Abstract

The routine use of whole genome sequencing (WGS) as a reference typing technique for epidemiology combined with the catalogued and extensive knowledge base of resistance-associated mutations means an initial susceptibility prediction can be derived from all cultured isolates in our laboratories based on WGS data alone. Preliminary work has confirmed, in our low-burden settings, these predictions are for first-line drugs, reproducible, robust with an accuracy similar to phenotypic drug susceptibility testing (pDST) and in many cases able to also predict the level of resistance (MIC). Routine screening for drug resistance by WGS results in approximately 80% of the isolates received being predicted as fully susceptible to the first-line drugs. Parallel testing with both WGS and pDST has demonstrated that routine pDST of genotypically fully susceptible isolates yields minimal additional information. Thus, rather than re-confirming all fully sensitive WGS-based predictions, we suggest that a more efficient use of available mycobacterial culture capacity in our setting is the development of a more extensive and detailed pDST targeted at any mono or multi-drug-resistant isolates identified by WGS screening. Phenotypic susceptibility retains a key role in the determination of an extended susceptibility profile for mono/multi-drugresistant isolates identified by WGS screening. The pDST information collected is also needed to support the development of future catalogues of resistance-associated mutations.

摘要

将全基因组测序(WGS)作为一种用于流行病学的参考分型技术,并结合已编目且广泛的耐药相关突变知识库,这意味着仅基于WGS数据,我们实验室中所有培养的分离株都可以得出初始药敏预测。初步工作已经证实,在我们负担较低的环境中,这些预测针对一线药物,具有可重复性、稳健性,准确性与表型药敏试验(pDST)相似,并且在许多情况下还能够预测耐药水平(最低抑菌浓度)。通过WGS进行耐药性常规筛查,结果显示约80%收到的分离株被预测对一线药物完全敏感。WGS和pDST的平行检测表明,对基因型完全敏感的分离株进行常规pDST只能产生极少的额外信息。因此,与其重新确认所有基于WGS的完全敏感预测,我们建议在我们的环境中更有效地利用可用的分枝杆菌培养能力,即针对通过WGS筛查鉴定出的任何单药或多药耐药分离株开展更广泛、更详细的pDST。表型药敏在确定通过WGS筛查鉴定出的单药/多药耐药分离株的扩展药敏谱方面仍起着关键作用。收集的pDST信息对于支持未来耐药相关突变目录的编制也很有必要。

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