Abstract
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 (NGS). 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/mL (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 Defi nite 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 vs 3.7 days for blood culture (proportional Odds 2.952, p= 0.02771), using a semi-parametric survival analysis. mcfDNA (log10) levels significantly declined (-0.3 MPM log10 units, 95% credible interval -0.45, -0.14) after surgical source control was performed (pre- vs post-procedure, 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.
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