High Cell-Free DNA Predicts Fatal Outcome among Staphylococcus aureus Bacteraemia Patients with Intensive Care Unit Treatment

Erik Forsblom,Janne Aittoniemi,Asko Järvinen,Reetta Huttunen,Juulia Jylhävä,Mikko Hurme,Eeva Ruotsalainen,Visa Helmijoki

doi:10.1371/journal.pone.0087741

Abstract

IntroductionAmong 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.Methods418 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.ResultsSAB 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.ConclusionHigh 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.

Highlights

Among patients with bacteraemia or sepsis the plasma cell-free DNA biomarker has prognostic value and Pitt bacteraemia scores predict outcome
Patient characteristics and cell-free DNA (cf-DNA) concentrations Altogether 430 Staphylococcus aureus bacteraemia (SAB) patients were included into the study but due to missing plasma samples the results of 418 patients are shown
The median cf-DNA concentrations at days 3 and 5 from the positive blood culture are shown in Table 1 stratified according to patient characteristics

Summary

Introduction

Among patients with bacteraemia or sepsis the plasma cell-free DNA (cf-DNA) biomarker has prognostic value and Pitt bacteraemia scores predict outcome. Staphylococcus aureus accounts for one fourth or one fifth of all bacteraemic infections worldwide [1,2,3,4] It is among the three most common pathogens in all types of infections in critically ill patients [5]. Biomarkers and intensive care scoring systems have been studied as clinical tools in the evaluation of severely ill patients with bacteraemia or sepsis and they may be used as an aid in risk stratification or as a surrogate marker for patient outcome, to identify a patient with increased probability of having a disease or a pathologic process, or to follow the treatment response [11,12,13,14]. The Pitt bacteraemia score system is known to reflect severity of illness among SAB patients [15,16] and the Pitt bacteraemia scores system was recently demonstrated to better predict mortality among ICU patients with sepsis as compared to APACHE II [12]

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