Circulating cell-free DNA is a highly versatile analyte that could be used to guide clinical decision making in patients with SAB.  A large number of small fragments of cfDNA naturally circulate in blood. In healthy individuals, cfDNA is predominantly derived from apoptosis of normal cells of the hematopoietic lineage, with additional contributions from other tissues.

One thousand to 10,000 genome equivalents of cfDNA can be isolated from just one mL of plasma. cfDNA offers an information-rich window into human physiology, with rapidly expanding clinical applications in prenatal testing, cancer diagnosis,the monitoring of infectious disease, allograft rejection, and immunosuppression after solid-organ transplantation. Our previous work has shown that cfDNA can predict clinical outcomes in patients with COVID-19, and also monitor for complications after allogeneic hematopoietic cell transplantation.

Because cfDNA methylation signatures can accurately determine its tissue of origin,this assay could be used to diagnose metastatic complications in patients with SAB and inform the need for additional diagnostic testing (e.g. abdominal ultrasound looking for splenic infarcts in patients with an increased proportion of splenic cell-free DNA). Simultaneously, it could help gauge the relative bacterial burden by quantifying the amount of S. aureus cell-free DNA in circulation. This assay could serve as a valuable tool to help guide decisions regarding IV to oral step down, as well as the total duration of antimicrobial treatment.

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All patients participating in the SNAP study, regardless of age, are potentially eligible to be recruited to this sub-study. We aim to recruit approximately 100 patients to this sub-study.

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