Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units.
Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units.
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DOI：
10.1186/s13073-021-00991-y
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发表时间：
2021-11-17
期刊：
影响因子：
12.3
通讯作者：
Edgeworth JD
中科院分区：
文献类型：
--
作者：
Charalampous T;Alcolea-Medina A;Snell LB;Williams TGS;Batra R;Alder C;Telatin A;Camporota L;Meadows CIS;Wyncoll D;Barrett NA;Hemsley CJ;Bryan L;Newsholme W;Boyd SE;Green A;Mahadeva U;Patel A;Cliff PR;Page AJ;O'Grady J;Edgeworth JD
临床宏基因组学（CMg）有可能从研究工具转化为常规服务，以改善抗菌治疗和感染控制决策。SARS-CoV-2大流行为实现这些益处提供了额外的动力，因为与重症监护能力的扩大有关的多重耐药（MDR）病原体的继发感染和医院传播的风险增加。在一项概念验证研究中，使用纳米孔测序对来自7个重症监护病房（ICU）的34名插管患者的43份呼吸道样本进行了评估，这些样本在第一次COVID-19大流行期间持续了9周。基于培养阳性和培养阴性样本，8小时CMg工作流程对细菌鉴定的敏感性分别为92%（95% CI，75-99%）和82%特异性（95% CI，57-96%）。CMg测序报告了是否存在肠球菌携带的β-内酰胺耐药基因，这些基因将在每种情况下修改最初的指南推荐的抗生素。CMg与定量PCR检测4份阳性和39份阴性烟曲霉的符合率为100%。使用24小时测序数据的分子分型鉴定了MDR-K。肺炎ST 307爆发，涉及4例患者和1例MDR-C。纹状体爆发涉及三个ICU的14名患者。CMg检测在同一天的实验室工作流程中提供准确的病原体检测和抗生素耐药性预测，第二天即可组装基因组进行基因组监测。在服务环境中提供这种技术可以从根本上改变管理ICU感染的多学科团队方法。改善初始靶向治疗和快速检测MDR病原体意外爆发的潜力证明了进一步加速CMg临床评估的合理性。在线版本包含补充材料，可通过10.1186/s13073-021-00991-y获得。
Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secondary infection and nosocomial transmission of multi-drug-resistant (MDR) pathogens linked with the expansion of critical care capacity. CMg using nanopore sequencing was evaluated in a proof-of-concept study on 43 respiratory samples from 34 intubated patients across seven intensive care units (ICUs) over a 9-week period during the first COVID-19 pandemic wave. An 8-h CMg workflow was 92% sensitive (95% CI, 75–99%) and 82% specific (95% CI, 57–96%) for bacterial identification based on culture-positive and culture-negative samples, respectively. CMg sequencing reported the presence or absence of β-lactam-resistant genes carried by Enterobacterales that would modify the initial guideline-recommended antibiotics in every case. CMg was also 100% concordant with quantitative PCR for detecting Aspergillus fumigatus from 4 positive and 39 negative samples. Molecular typing using 24-h sequencing data identified an MDR-K. pneumoniae ST307 outbreak involving 4 patients and an MDR-C. striatum outbreak involving 14 patients across three ICUs. CMg testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance. The provision of this technology in a service setting could fundamentally change the multi-disciplinary team approach to managing ICU infections. The potential to improve the initial targeted treatment and rapidly detect unsuspected outbreaks of MDR-pathogens justifies further expedited clinical assessment of CMg. The online version contains supplementary material available at 10.1186/s13073-021-00991-y.
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