High cell-free DNA predicts fatal outcome among Staphylococcus aureus bacteraemia patients with intensive care unit treatment.

Abstract

Among patients with bacteraemia or sepsis the plasma cell-free DNA (cf-DNA) biomarker has prognostic value and Pitt bacteraemia scores predict outcome. We evaluated the prognostic value of plasma cf-DNA in patients with Staphylococcus aureus bacteraemia (SAB) treated in the ICU or in the general ward. 418 adult patients with positive blood culture for S. aureus were prospectively followed for 90 days. SAB patients were grouped according to ICU treatment: 99 patients were treated in ICU within 7 days of documented SAB whereas 319 patients were managed outside ICU. Pitt bacteraemia scores were assessed at hospital arrival and cf-DNA was measured at days 3 and 5 from positive blood culture. SAB patients with high Pitt bacteraemia scores and ICU treatment presented higher cf-DNA values as compared to SAB patients with low Pitt bacteraemia scores and non-ICU treatment at both days 3 and 5. Among ICU patients cf-DNA >1.99 µg/ml at day 3 predicted death with a sensitivity of 67% and a specificity of 77% and had an AUC in receiver operating characteristic analysis of 0.71 (p<0.01). The cut-off cf-DNA >1.99 µg/ml value demonstrated a strong association to high Pitt bacteraemia scores (≥ 4 points) (p<0.000). After controlling for all prognostic markers, Pitt bacteraemia scores ≥ 4 points at hospital admission (OR 4.47, p<0.000) and day 3 cf-DNA (OR 3.56, p<0.001) were the strongest factors significantly predicting outcome in ICU patients. cf-DNA at day 5 did not predict fatal outcome. High cf-DNA concentrations were observed among patients with high Pitt bacteraemia scores and ICU treatment. Pitt bacteraemia scores (≥ 4 points) and cf-DNA at day 3 from positive blood culture predicted death among SAB patients in ICU and were found to be independent prognostic markers. cf-DNA had no prognostic value among non-ICU patients.