Biomarker of neutrophil extracellular traps is associated with deep-seated infections and predicts mortality and cardiovascular morbidity in commensal streptococcal bacteremia.

Abstract

Neutrophil extracellular traps (NETs) play important roles in sepsis and deep-seated infections, but whether NET formation correlates with clinical outcomes of patients with streptococcal bloodstream infections (BSIs) is unclear. We analyzed serum levels of complexes of myeloperoxidase and DNA (MPO-DNA) in patients with streptococcal-BSIs. Invitro assay of NET induction by serum from BSI patients was performed. MPO-DNA values for the Streptococci-BSI group (n=59) were significantly higher than those for healthy controls (p<0.00001) and matched control groups (n=59, p=0.004). The rate of higher MPO-DNA levels (>1.87μg/mL) were higher in abscess-prone streptococcal groups (streptococcus milleri group) (72.2% vs. 52.5%, p=0.02). For patients with BSIs due to highly infective endocarditis (IE)-prone pathogens, the values of serum MPO-DNA were also higher in patients diagnosed of IE compared to their counterparts (p=0.009). Notably, serum from patients with leukopenia could induce higher amounts of invitro NET formation, despite having low MPO-DNA levels, suggesting that NET formation could be influenced by WBC counts. Therefore, we combined WBC counts with MPO-DNA to predict all-cause 30-day mortality in patients with commensal streptococcal-BSIs. The mortality risk was lowest among patients who had neither high MPO-DNA levels nor abnormal WBC counts (p=0.058). Furthermore, this group of patients also had a favorable composite outcome consisting of major adverse cardiovascular events (MACE) and all-cause mortality (p=0.026). Together, these study data suggested that serum MPO-DNA can be a biomarker for predicting a composite outcome consisting of MACE and all-cause mortality in patients with commensal streptococcal-BSIs.