Control of hospital-associated Enterococcus faecium infection is a strenuous task due to the difficulty of identifying transmission routes and the persistence of this nosocomial pathogen despite the implementation of infection control measures that have been successful with other important nosocomial pathogens. This study provides a comprehensive analysis of over one hundred E. faecium isolates collected from 66 cancer patients at the University of Arkansas for Medical Sciences (UAMS) between June, 2018 and May, 2019. In the top-down approach used in this study we employed, in addition to the 106 E. faecium UAMS isolates, a filtered set of 2167 E. faecium strains from the GenBank database to assess the current population structure of E. faecium species and, consequently, to identify the lineages associated with our clinical isolates. We then evaluated the antibiotic resistance and virulence profiles of hospital-associated strains from the species pool, focusing on antibiotics of last resort, in order to establish an updated classification of high-risk and multidrug-resistant nosocomial clones. Further investigation of the clinical isolates collected from UAMS patients using whole genome sequencing analytical methodologies (cgMLST, coreSNP and phylogenomics), with the addition of patient epidemiological data, revealed a polyclonal outbreak of three sequences types occurring simultaneously in different patient wards. The integration of genomic and epidemiological data collected from the patients increased our understanding of the relationships and transmission dynamics of the E. faecium isolates. Our study provides new insights into genomic surveillance of E. faecium to assist in monitoring and further limiting the spread of multidrug-resistant E. faecium.

The authors have declared no competing interest.

This work was supported by the University of Arkansas for Medical Sciences (UAMS) College of Medicine Barton Pilot Grant FY19 and FY21 program; the UAMS Translational Research Institute (UL1 TR003107) through the NIH National Center for 597 Advancing Translational Sciences and the National Science Foundation under award no. OIA-1946391; and the National Institute of Allergy and Infectious Disease (NIAID) under award no. R21AI169138. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the Institutional Review Board of University of Arkansas for Medical Sciences (IRB No. 228137).

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Raw sequencing data, assembly and functional annotations for the isolates used in this study are available under the BioProject accession numbers, PRJNA518133, PRJNA735268 and PRJNA520878, of NCBI database.