The Journal of infectious diseases · 2025
Clinical and Genomic Characterization of Recalcitrant Enterococcal Bacteremia: A Multicenter Prospective Cohort Study (VENOUS).
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Simar Shelby R, Tran Truc T, Rydell Kirsten B, Atterstrom Rachel L, Sahasrabhojane Pranoti V, Dinh An Q, Schettino Marissa G, Slanis Haley S, Deyanov Alex E, DeTranaltes Andie M, Axell-House Dierdre B, Miller William R, Munita Jose M, Tobys David, Seifert Harald, Biehl Lena M, Zervos Marcus, Suleyman Geehan, Kaur Jagjeet, Warzocha Victoria, Rosa Rossana, Cifuentes Renzo O, Abbo Lilian M, Shimose Luis, Liu Catherine, Nguyen Katherine, Miller Ashleigh, Shelburne Samuel A, Hanson Blake M, Arias Cesar A
Аннотация
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.
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.