Nosocomial acquisition and transmission of vancomycin-resistant Enterococcus faecium (VREfm) is the driver for E. faecium carriage in hospitalized patients, which, in turn, is a risk factor for invasive infection in immunocompromised patients. In the present study, we provide a comprehensive picture of E. faecium transmission in an entire sampled patient population using a sequence-driven approach. We prospectively identified and followed 149 haematology patients admitted to a hospital in England for 6 months. Patient stools (n = 376) and environmental swabs (n = 922) were taken at intervals and cultured for E. faecium. We sequenced 1,560 isolates (1,001 stool, 559 environment) and focused our genomic analyses on 1,477 isolates (95%) in the hospital-adapted clade A1. Of 101 patients who provided two or more stool samples, 40 (40%) developed E. faecium carriage after admission based on culture, compared with 64 patients (63%) based on genomic analysis (73% VREfm). Half of 922 environmental swabs (447, 48%) were positive for VREfm. Network analysis showed that, of 111 patients positive for the A1 clade, 67 had strong epidemiological and genomic links with at least one other patient and/or their direct environment, supporting nosocomial transmission. Six patients (3.4%) developed an invasive E. faecium infection from their own gut-colonizing strain, which was preceded by nosocomial acquisition of the infecting isolate in half of these. Two informatics approaches (subtype categorization to define phylogenetic clusters and the development of an SNP cut-off for transmission) were central to our analyses, both of which will inform the future translation of E. faecium sequencing into routine outbreak detection and investigation. In conclusion, we showed that carriage and environmental contamination by the hospital-adapted E. faecium lineage were hyperendemic in our study population and that improved infection control measures will be needed to reduce hospital acquisition rates.

耐万古霉素粪肠球菌(VREfm) 的医院获得和传播是住院患者携带粪肠球菌的驱动因素，而这反过来又是免疫功能低下患者侵袭性感染的危险因素。在本研究中，我们使用序列驱动的方法提供了整个采样患者群体中粪肠球菌传播的全面情况。我们前瞻性地识别并跟踪了 149 名在英格兰一家医院住院的血液病患者，为期 6 个月。每隔一段时间采集患者粪便 ( n  = 376) 和环境拭子 ( n  = 922) 并培养粪肠球菌. 我们对 1,560 个分离株（1,001 个粪便，559 个环境）进行了测序，并将我们的基因组分析集中在医院适应进化枝 A1 中的 1,477 个分离株（95%）上。在提供两个或更多粪便样本的 101 名患者中，40 名（40%）在入院后根据培养结果出现粪肠球菌携带，而根据基因组分析（73% VREfm），有 64 名患者（63%）在入院后出现粪肠球菌携带。922 个环境拭子中有一半（447 个，48%）对 VREfm 呈阳性。网络分析显示，在 A1 进化枝呈阳性的 111 名患者中，67 名与至少一名其他患者和/或其直接环境有很强的流行病学和基因组联系，支持医院传播。6 名患者 (3.4%) 出现侵入性粪肠球菌来自他们自己的肠道定植菌株的感染，在此之前，其中一半是在医院获得了感染分离物。两种信息学方法（定义系统发育簇的亚型分类和传播 SNP 截止值的开发）是我们分析的核心，这两种方法都将为未来将粪肠球菌测序转化为常规爆发检测和调查提供信息。总之，我们表明医院适应的粪肠球菌谱系的携带和环境污染在我们的研究人群中是高度流行的，需要改进感染控制措施来降低医院感染率。