Clinical and Genomic Characterization of Recalcitrant Enterococcal Bacteremia: A Multicenter Prospective Cohort Study (VENOUS)
Journal
The Journal of Infectious Diseases
ISSN
0022-1899
Date Issued
2025-07-08
Author(s)
Shelby R Simar
Truc T Tran
Kirsten B Rydell
Rachel L Atterstrom
Pranoti V Sahasrabhojane
An Q Dinh
Marissa G Schettino
Haley S Slanis
Alex E Deyanov
Andie M DeTranaltes
Dierdre B Axell-House
William R Miller
David Tobys
Harald Seifert
Lena M Biehl
Marcus Zervos
Geehan Suleyman
Jagjeet Kaur
Victoria Warzocha
Rossana Rosa
Renzo O Cifuentes
Lilian M Abbo
Luis Shimose
Catherine Liu
Katherine Nguyen
Ashleigh Miller
Samuel A Shelburne
Blake M Hanson
Cesar A Arias
Type
journal-article
Abstract
Background: 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. Methods: Bacteremia episodes were considered "persistent" if there was a lack of clearance on day four while receiving >= 48 hours of active therapy and recurrent if there was clearance during hospitalization with a subsequent positive culture (collectively, "recalcitrant" 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. Findings: 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. E. faecalis 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 E. faecium and E. faecalis index and persistent isolates, suggesting species-specific adaptation. Discussion: 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 E. faecium 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.
Cite this document
Simar, S. R., Tran, T. T., Rydell, K. B., Atterstrom, R. L., Sahasrabhojane, P. V., Dinh, A. Q., Schettino, M. G., Slanis, H. S., Deyanov, A. E., DeTranaltes, A. M., Axell-House, D. B., Miller, W. R., Munita, J. M., Tobys, D., Seifert, H., Biehl, L. M., Zervos, M., Suleyman, G., Kaur, J., … Arias, C. A. (2025). Clinical and genomic characterization of recalcitrant enterococcal bacteremia: A multicenter prospective cohort study(Venous). The Journal of Infectious Diseases, jiaf358. https://doi.org/10.1093/infdis/jiaf358