Microbial Cell-Free DNA Identifies Etiology of Bloodstream Infections, Persists Longer Than Conventional Blood Cultures, and its Duration of Detection is Associated with Metastatic Infection in Patients with Staphylococcus aureus and Gram-Negative Bacteremia.

Eichenberger, Emily M; de Vries, Christiaan R; Ruffin, Felicia; Sharma-Kuinkel, Batu; Park, Lawrence; Hong, David; Scott, Erick R; Blair, Lily; Degner, Nicholas; Hollemon, Desiree H; Blauwkamp, Timothy A; Ho, Carine; Seng, Hon; Shah, Pratik; Wanda, Lisa; Fowler, Vance G; Ahmed, Asim A

Microbial Cell-Free DNA Identifies Etiology of Bloodstream Infections, Persists Longer Than Conventional Blood Cultures, and its Duration of Detection is Associated with Metastatic Infection in Patients with Staphylococcus aureus and Gram-Negative Bacteremia.

dc.contributor.author	Eichenberger, Emily M
dc.contributor.author	de Vries, Christiaan R
dc.contributor.author	Ruffin, Felicia
dc.contributor.author	Sharma-Kuinkel, Batu
dc.contributor.author	Park, Lawrence
dc.contributor.author	Hong, David
dc.contributor.author	Scott, Erick R
dc.contributor.author	Blair, Lily
dc.contributor.author	Degner, Nicholas
dc.contributor.author	Hollemon, Desiree H
dc.contributor.author	Blauwkamp, Timothy A
dc.contributor.author	Ho, Carine
dc.contributor.author	Seng, Hon
dc.contributor.author	Shah, Pratik
dc.contributor.author	Wanda, Lisa
dc.contributor.author	Fowler, Vance G
dc.contributor.author	Ahmed, Asim A
dc.date.accessioned	2022-02-01T19:55:40Z
dc.date.available	2022-02-01T19:55:40Z
dc.date.issued	2021-08-30
dc.date.updated	2022-02-01T19:55:39Z
dc.description.abstract	Background Microbial cell-free DNA (mcfDNA) sequencing of plasma can identify presence of a pathogen in a host. This study evaluated the duration of pathogen detection by mcfDNA sequencing vs. conventional blood culture in patients with bacteremia. Methods Blood samples from patients with culture-confirmed bloodstream infection were collected within 24 hours of the index positive blood culture and 48 to 72 hours thereafter. mcfDNA was extracted from plasma and next-generation sequencing (NGS) applied. Reads were aligned against a curated pathogen database. Statistical significance was defined with Bonferroni adjustment for multiple comparisons (p < 0.0033). Results A total of 175 patients with Staphylococcus aureus bacteremia (SAB; n=66), Gram-negative bacteremia (GNB; n=74), or non-infected controls (n=35) were enrolled. The overall sensitivity of mcfDNA sequencing compared to index blood culture was 89.3% (125/140) and the specificity was 74.3%. Among patients with bacteremia, pathogen specific mcfDNA remained detectable for significantly longer than conventional blood cultures (median 15 days vs. 2 days; p<0.0001). Each additional day of mcfDNA detection significantly increased the odds of metastatic infection (Odds Ratio [OR]: 2.89; 95% Confidence Interval [CI]: 1.53-5.46; p=0.0011). Conclusions Pathogen mcfDNA identified the bacterial etiology of bloodstream infection for a significantly longer interval than conventional cultures, and its duration of detection was associated with increased risk for metastatic infection. mcfDNA could play a role in the diagnosis of partially treated endovascular infections.
dc.identifier	6359848
dc.identifier.issn	1058-4838
dc.identifier.issn	1537-6591
dc.identifier.uri	https://hdl.handle.net/10161/24323
dc.language	eng
dc.publisher	Oxford University Press (OUP)
dc.relation.ispartof	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
dc.relation.isversionof	10.1093/cid/ciab742
dc.subject	Microbial cell-free diagnostics
dc.subject	bacteremia
dc.title	Microbial Cell-Free DNA Identifies Etiology of Bloodstream Infections, Persists Longer Than Conventional Blood Cultures, and its Duration of Detection is Associated with Metastatic Infection in Patients with Staphylococcus aureus and Gram-Negative Bacteremia.
dc.type	Journal article
duke.contributor.orcid	Ruffin, Felicia\|0000-0003-2176-6462
duke.contributor.orcid	Fowler, Vance G\|0000-0002-8048-0897
pubs.organisational-group	Duke
pubs.organisational-group	School of Medicine
pubs.organisational-group	Basic Science Departments
pubs.organisational-group	Clinical Science Departments
pubs.organisational-group	Institutes and Centers
pubs.organisational-group	Molecular Genetics and Microbiology
pubs.organisational-group	Medicine
pubs.organisational-group	Medicine, Infectious Diseases
pubs.organisational-group	Duke Clinical Research Institute
pubs.publication-status	Published