TY - JOUR
T1 - Clinical and Genomic Characterization of Recalcitrant Enterococcal Bacteremia
T2 - A Multicenter Prospective Cohort Study (VENOUS)
AU - Simar, Shelby R.
AU - Tran, Truc T.
AU - Rydell, Kirsten B.
AU - Atterstrom, Rachel L.
AU - Sahasrabhojane, Pranoti V.
AU - Dinh, An Q.
AU - Schettino, Marissa G.
AU - Slanis, Haley S.
AU - Deyanov, Alex E.
AU - DeTranaltes, Andie M.
AU - Axell-House, Dierdre B.
AU - Miller, William R.
AU - Munita, Jose M.
AU - Tobys, David
AU - Seifert, Harald
AU - Biehl, Lena M.
AU - Zervos, Marcus
AU - Suleyman, Geehan
AU - Kaur, Jagjeet
AU - Warzocha, Victoria
AU - Rosa, Rossana
AU - Cifuentes, Renzo O.
AU - Abbo, Lilian M.
AU - Shimose, Luis
AU - Liu, Catherine
AU - Nguyen, Katherine
AU - Miller, Ashleigh
AU - Shelburne, Samuel A.
AU - Hanson, Blake M.
AU - Arias, Cesar A.
N1 - © The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].
PY - 2025/12/15
Y1 - 2025/12/15
N2 - 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 4 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 nonrecalcitrant bacteremia patients was chosen in a 2:1 control to case ratio. Isolates were subjected to short- and long-read whole-genome sequencing. Hybrid assemblies were created using a custom pipeline. Results A total of 46 recalcitrant infections from 41 patients were identified. Patients with persistent bacteremia were more often admitted to the intensive care unit upon admission relative to controls. Enterococcus 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 Enterococcus 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 versus persistent isolates revealed that E. faecium may be genetically preadapted to cause persistent infection, and site-specific structural variation during infection suggests the role of differential gene expression in adaptation and persistence. These data lay groundwork for future studies to define signatures of enterococcal adaptation during bacteremia.
AB - 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 4 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 nonrecalcitrant bacteremia patients was chosen in a 2:1 control to case ratio. Isolates were subjected to short- and long-read whole-genome sequencing. Hybrid assemblies were created using a custom pipeline. Results A total of 46 recalcitrant infections from 41 patients were identified. Patients with persistent bacteremia were more often admitted to the intensive care unit upon admission relative to controls. Enterococcus 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 Enterococcus 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 versus persistent isolates revealed that E. faecium may be genetically preadapted to cause persistent infection, and site-specific structural variation during infection suggests the role of differential gene expression in adaptation and persistence. These data lay groundwork for future studies to define signatures of enterococcal adaptation during bacteremia.
KW - Enterococcus; bacteremia
KW - genomic adaptation
KW - persistent infection
UR - https://www.scopus.com/pages/publications/105025415283
UR - https://www.scopus.com/inward/citedby.url?scp=105025415283&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiaf358
DO - 10.1093/infdis/jiaf358
M3 - Article
C2 - 40629152
AN - SCOPUS:105025415283
SN - 0022-1899
VL - 232
SP - 1351
EP - 1364
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -