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, Jose M Munita, 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
{"title":"顽固性肠球菌菌血症的临床和基因组特征：一项多中心前瞻性队列研究（静脉）。","authors":"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, Jose M Munita, 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","doi":"10.1093/infdis/jiaf358","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical and Genomic Characterization of Recalcitrant Enterococcal Bacteremia: A Multicenter Prospective Cohort Study (VENOUS).\",\"authors\":\"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, Jose M Munita, 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\",\"doi\":\"10.1093/infdis/jiaf358\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Discussion: </strong>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.</p>\",\"PeriodicalId\":50179,\"journal\":{\"name\":\"Journal of Infectious Diseases\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-07-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/infdis/jiaf358\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/infdis/jiaf358","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Clinical and Genomic Characterization of Recalcitrant Enterococcal Bacteremia: A Multicenter Prospective Cohort Study (VENOUS).
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.
期刊介绍：
Published continuously since 1904, The Journal of Infectious Diseases (JID) is the premier global journal for original research on infectious diseases. The editors welcome Major Articles and Brief Reports describing research results on microbiology, immunology, epidemiology, and related disciplines, on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune responses. JID is an official publication of the Infectious Diseases Society of America.
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