title: The detection of microbial DNA but not cultured bacteria is associated with increased mortality in patients with suspected sepsis-a prospective multi-centre European observational study.
abstract: OBJECTIVE
  Blood culture results inadequately stratify the mortality risk in critically ill patients with sepsis. We sought to establish the prognostic significance of the presence of microbial DNA in the bloodstream of patients hospitalized with suspected sepsis.
  
  
  METHODS
  We analysed the data collected during the Rapid Diagnosis of Infections in the Critically Ill (RADICAL) study, which compared a novel culture-independent PCR/electrospray ionization-mass spectrometry (ESI-MS) assay with standard microbiological testing. Patients were eligible for the study if they had suspected sepsis and were either hospitalized or were referred to one of nine intensive care units from six European countries. The blood specimen for PCR/ESI-MS assay was taken along with initial blood culture taken for clinical indications.
  
  
  RESULTS
  Of the 616 patients recruited to the RADICAL study, 439 patients had data on outcome, results of the blood culture and PCR/ESI-MS assay available for analysis. Positive blood culture and PCR/ESI-MSI result was found in 13% (56/439) and 40% (177/439) of patients, respectively. Either a positive blood culture (p 0.01) or a positive PCR/ESI-MS (p 0.005) was associated with higher SOFA scores on enrolment to the study. There was no difference in 28-day mortality observed in patients who had either positive or negative blood cultures (35% versus 32%, p 0.74). However, in patients with a positive PCR/ESI-MS assay, mortality was significantly higher in comparison to those with a negative result (42% versus 26%, p 0.001).
  
  
  CONCLUSIONS
  Presence of microbial DNA in patients with suspected sepsis might define a patient group at higher risk of death.
authors.affiliation: Department of Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Electronic address: m.odwyer@qmul.ac.uk.
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Dwyer
authors.affiliation: Adult Critical Care Unit, Royal London Hospital, Barts Health NHS Trust, London, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Starczewska
authors.affiliation: Genomic Research Laboratory, Department of Internal Medicine, Service of Infectious Diseases, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Schrenzel
authors.affiliation: Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Zacharowski
authors.affiliation: Ibis Biosciences, Abbott, Carlsbad, CA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Ecker
authors.affiliation: Ibis Biosciences, Abbott, Carlsbad, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Sampath
authors.affiliation: Division of Critical Care, University College London Hospitals NIHR Biomedical Research Centre and Bloomsbury Institute of Intensive Care Medicine, University College Hospital, London, United Kingdom.
authors.forename: D
authors.initials: D
authors.lastname: Brealey
authors.affiliation: Division of Critical Care, University College London Hospitals NIHR Biomedical Research Centre and Bloomsbury Institute of Intensive Care Medicine, University College Hospital, London, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Singer
authors.affiliation: Department of Anaesthesiology and Critical Care, Val de Grâce Military Hospital, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Libert
authors.affiliation: Barts and The London School of Medicine and Dentistry, Queen Mary University of London and Barts Health NHS Trust, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Wilks
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: J-L
authors.initials: JL
authors.lastname: Vincent
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001419:Bacteria / Q000302:isolation & purification*; D001431:Bacteriological Techniques / Q000379:methods*; D001769:Blood / Q000382:microbiology*; D016638:Critical Illness; D004269:DNA, Bacterial / Q000097:blood*; D042241:Early Diagnosis; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D018805:Sepsis / Q000175:diagnosis* / Q000401:mortality*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial
keywords: Critically ill; Culture-independent; Early diagnosis; Infection; Molecular detection; Mortality