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Microbial Cell-Free DNA Identifies the Causative Pathogen in Infective Endocarditis and Remains Detectable Longer Than Conventional Blood Culture in Patients with Prior Antibiotic Therapy.
BACKGROUND: The diagnosis of infective endocarditis (IE) can be difficult, particularly if blood cultures fail to yield a pathogen. This study evaluates the potential utility of microbial cell-free DNA (mcfDNA) as a tool to identify the microbial etiology of IE. METHODS: Blood samples from patients with suspected IE were serially collected. mcfDNA was extracted from plasma and underwent next-generation sequencing. Reads were aligned against a library containing DNA sequences belonging to >1400 different pathogens. mcfDNA from organisms present above a statistical threshold were reported and quantified in molecules per milliliter (MPM). Additional mcfDNA was collected on each subject every 2-3 days for a total of 7 collections or until discharge. RESULTS: Of 30 enrolled patients with suspected IE, 23 had definite IE, 2 had possible IE, and IE was rejected in 5 patients by modified Duke Criteria. Only the 23 patients with definite IE were included for analysis. Both mcfDNA and blood cultures achieved a sensitivity of 87%. The median duration of positivity from antibiotic treatment initiation was estimated to be approximately 38.1 days for mcfDNA versus 3.7 days for blood culture (proportional odds, 2.952; P = .02771), using a semiparametric survival analysis. mcfDNA (log10) levels significantly declined (-0.3 MPM log10 units, 95% credible interval -0.45 to -0.14) after surgical source control was performed (pre- vs postprocedure, posterior probability >0.99). CONCLUSION: mcfDNA accurately identifies the microbial etiology of IE. Sequential mcfDNA levels may ultimately help to individualize therapy by estimating a patient's burden of infection and response to treatment.
Duke Scholars
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Related Subject Headings
- Microbiology
- Humans
- Endocarditis, Bacterial
- Endocarditis
- Cell-Free Nucleic Acids
- Blood Culture
- Anti-Bacterial Agents
- 3202 Clinical sciences
- 11 Medical and Health Sciences
- 06 Biological Sciences
Citation
![Journal cover image](https://secure.syndetics.com/index.aspx?isbn=/lc.gif&issn=1537-6591&client=dukeuniv)
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Microbiology
- Humans
- Endocarditis, Bacterial
- Endocarditis
- Cell-Free Nucleic Acids
- Blood Culture
- Anti-Bacterial Agents
- 3202 Clinical sciences
- 11 Medical and Health Sciences
- 06 Biological Sciences