Circulating bacterial DNA is associated with disease severity in patients with S. aureus bacteremia

Abstract

Abstract Staphylococcus aureus bacteremia is a leading cause of morbidity and mortality and yet tools to assess severity of infection and response to treatment are still lacking. This study aimed to establish a link between bacterial DNA quantified in blood and clinical severity in bacteremic patients. We developed a workflow coupled with a highly sensitive quantitative PCR method to quantify S. aureus bacterial DNA. This assay was used to measure whole blood S. aureus DNA (SA-DNA) and plasma-derived S. aureus cell-free DNA (SA-cfDNA) in a set of longitudinal samples from 45 patients with confirmed S. aureus bacteremia. SA-DNA was detectable at baseline and declined following treatment with antibiotics. Notably, baseline SA-DNA correlated with disease severity and levels were sustained in cases of complicated infections versus with non-complicated infections. In addition, plasma-derived S. aureus cell-free DNA could be readily detected in bacteremic patients and showed concordance with whole blood SA-DNA. High levels of SA-DNA and SA-cfDNA were associated with metrics of clinical severity, including longer durations of treatment, elevated white blood cell count, and positive blood cultures. Taken together, these data suggest that circulating bacterial DNA is more reflective of whole body bacterial load than blood culture and may aid in monitoring clearance of tissue reservoirs of infection during antibiotic therapy.