{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T09:46:50Z","timestamp":1775987210866,"version":"3.50.1"},"posted":{"date-parts":[[2025,4,6]]},"group-title":"Genomics","reference-count":52,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T00:00:00Z","timestamp":1743897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Patients with recalcitrant enterococcal bloodstream infections are at greater risk of adverse outcomes. We identified patients in the 2016-2022 Vancomycin-Resistant Enterococcal Bacteremia Outcomes Study (VENOUS) cohort experiencing recalcitrant bloodstream infections for further clinical and genomic characterization.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Bacteremia episodes were considered \u201cpersistent\u201d if there was a lack of clearance on day four while receiving \u2265 48 hours of active therapy and recurrent if there was clearance during hospitalization with a subsequent positive culture (collectively, \u201crecalcitrant\u201d bacteremia). A matched comparison group of non-recalcitrant bacteremia patients was chosen in a 2:1 control:case ratio. Isolates were subjected to short- and long-read whole-genome sequencing. Hybrid assemblies were created using a custom pipeline.\n                    <jats:italic>Findings.<\/jats:italic>\n                    A total of 46 recalcitrant infections from 41 patients were identified. Patients with persistent bacteremia were more often admitted to the ICU upon admission relative to controls.\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    strains causing persistent infections had a significantly higher proportion of genes associated with carbohydrate utilization relative to controls. Representation of functional groups associated with mutated genes was disparate between\n                    <jats:italic>E. faecium<\/jats:italic>\n                    and\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    index and persistent isolates, suggesting species-specific adaptation.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>\n                    Enterococcal isolates causing recalcitrant bacteremia were genomically diverse, indicating that strain-specific signatures are not drivers of persistence. However, comparisons of index vs. persistent isolates revealed that\n                    <jats:italic>E. faecium<\/jats:italic>\n                    may be genetically pre-adapted to cause persistent infection, and site-specific structural variation during infection suggests the role of differential gene expression in adaptation and persistence. This data lays groundwork for future studies to define signatures of enterococcal adaptation during bacteremia.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.04.01.645485","type":"posted-content","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T02:00:12Z","timestamp":1743991212000},"source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Genomic Characterization of Recalcitrant Enterococcal Bacteremia: A Multicenter Prospective Cohort Study (VENOUS)"],"prefix":"10.64898","author":[{"given":"Shelby R.","family":"Simar","sequence":"first","affiliation":[{"name":"Center for Infectious Diseases, UTHealth-Houston School of Public Health, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Truc T.","family":"Tran","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Houston Methodist Hospital, Houston, TX, USA"},{"name":"Center for Infectious Diseases, Houston Methodist Research Institute, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten B.","family":"Rydell","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Houston Methodist Hospital, Houston, TX, USA"},{"name":"Center for Infectious Diseases, Houston Methodist Research Institute, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel L.","family":"Atterstrom","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Houston Methodist Hospital, Houston, TX, USA"},{"name":"Center for Infectious Diseases, Houston Methodist Research Institute, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pranoti V.","family":"Sahasrabhojane","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 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