Clinical pilot of bacterial transcriptional profiling as a combined genotypic and phenotypic antimicrobial susceptibility test.

IF 6.1 2区 医学 Q1 MICROBIOLOGY
Journal of Clinical Microbiology Pub Date : 2024-11-13 Epub Date: 2024-10-21 DOI:10.1128/jcm.00997-24
E L Young, D J Roach, M A Martinsen, G E G McGrath, N R Holbrook, H E Cho, E Y Seyoum, V M Pierce, R P Bhattacharyya
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引用次数: 0

Abstract

Antimicrobial resistance is a growing health threat, but standard methods for determining antibiotic susceptibility are slow and can delay optimal treatment, which is especially consequential in severe infections such as bacteremia. Novel approaches for rapid susceptibility profiling have emerged that characterize either bacterial response to antibiotics (phenotype) or detect specific resistance genes (genotype). Genotypic and Phenotypic AST through RNA detection (GoPhAST-R) is a novel assay, performed directly on positive blood cultures, that integrates rapid transcriptional response profiling with the detection of key resistance gene transcripts, thereby providing simultaneous data on both phenotype and genotype. Here, we performed the first clinical pilot of GoPhAST-R on 42 positive blood cultures: 26 growing Escherichia coli, 15 growing Klebsiella pneumoniae, and 1 with both. An aliquot of each positive blood culture was exposed to nine different antibiotics, lysed, and underwent rapid transcriptional profiling on the NanoString platform; results were analyzed using an in-house susceptibility classification algorithm. GoPhAST-R achieved 95% overall agreement with standard antimicrobial susceptibility testing methods, with the highest agreement for beta-lactams (98%) and the lowest for fluoroquinolones (88%). Epidemic resistance genes including the extended spectrum beta-lactamase blaCTX-M-15 and the carbapenemase blaKPC were also detected within the population. This study demonstrates the clinical feasibility of using transcriptional response profiling for rapid resistance determination, although further validation with larger and more diverse bacterial populations will be essential in future work. GoPhAST-R represents a promising new approach for rapid and comprehensive antibiotic susceptibility testing in clinical settings.IMPORTANCEExposure to antibiotics causes differential transcriptional signatures in susceptible vs resistant bacteria. These differences can be leveraged to rapidly predict resistance profiles of Escherichia coli and Klebsiella pneumoniae in clinically positive blood cultures.

细菌转录谱分析作为基因型和表型抗菌药敏感性联合检测的临床试验。
抗生素耐药性对健康的威胁与日俱增,但确定抗生素敏感性的标准方法进展缓慢,可能会延误最佳治疗时间,尤其是在菌血症等严重感染中。新出现的快速易感性分析方法可以描述细菌对抗生素的反应(表型)或检测特定的耐药基因(基因型)。通过 RNA 检测基因型和表型 AST(GoPhAST-R)是一种直接在阳性血液培养物上进行的新型检测方法,它将快速转录反应谱分析与关键耐药基因转录本检测结合在一起,从而同时提供表型和基因型数据。在此,我们对 42 份阳性血液培养物进行了 GoPhAST-R 的首次临床试验:其中 26 份培养出大肠埃希菌,15 份培养出肺炎克雷伯菌,1 份同时培养出两种细菌。每个阳性血培养物的等分试样都暴露于 9 种不同的抗生素,裂解后在 NanoString 平台上进行快速转录剖析;使用内部药敏性分类算法对结果进行分析。GoPhAST-R 与标准抗菌素药敏测试方法的总体一致性达到 95%,其中β-内酰胺类药物的一致性最高(98%),氟喹诺酮类药物的一致性最低(88%)。在人群中还检测到了流行性耐药基因,包括广谱β-内酰胺酶blaCTX-M-15和碳青霉烯酶blaKPC。这项研究证明了利用转录反应图谱进行快速耐药性测定的临床可行性,不过在今后的工作中还必须利用更大、更多样化的细菌群体进行进一步验证。GoPhAST-R 是在临床环境中进行快速、全面抗生素敏感性测试的一种很有前途的新方法。重要意义暴露于抗生素会导致易感细菌和耐药细菌的转录特征出现差异。利用这些差异可以快速预测临床阳性血液培养物中大肠埃希菌和肺炎克雷伯菌的耐药性特征。
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 Clinical Microbiology
Journal of Clinical Microbiology 医学-微生物学
CiteScore
17.10
自引率
4.30%
发文量
347
审稿时长
3 months
期刊介绍: The Journal of Clinical Microbiology® disseminates the latest research concerning the laboratory diagnosis of human and animal infections, along with the laboratory's role in epidemiology and the management of infectious diseases.
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