title: The Host Response in Patients with Sepsis Developing Intensive Care Unit-acquired Secondary Infections.
abstract: Sepsis can be complicated by secondary infections. We explored the possibility that patients with sepsis developing a secondary infection while in the intensive care unit (ICU) display sustained inflammatory, vascular, and procoagulant responses.
  
  
  
  To compare systemic proinflammatory host responses in patients with sepsis who acquire a new infection with those who do not.
  
  
  
  Consecutive patients with sepsis with a length of ICU stay greater than 48 hours were prospectively analyzed for the development of ICU-acquired infections. Twenty host response biomarkers reflective of key pathways implicated in sepsis pathogenesis were measured during the first 4 days after ICU admission and at the day of an ICU-acquired infection or noninfectious complication.
  
  
  
  Of 1,237 admissions for sepsis (1,089 patients), 178 (14.4%) admissions were complicated by ICU-acquired infections (at Day 10 [6-13], median with interquartile range). Patients who developed a secondary infection showed higher disease severity scores and higher mortality up to 1 year than those who did not. Analyses of biomarkers in patients who later went on to develop secondary infections revealed a more dysregulated host response during the first 4 days after admission, as reflected by enhanced inflammation, stronger endothelial cell activation, a more disturbed vascular integrity, and evidence for enhanced coagulation activation. Host response reactions were similar at the time of ICU-acquired infectious or noninfectious complications.
  
  
  
  Patients with sepsis who developed an ICU-acquired infection showed a more dysregulated proinflammatory and vascular host response during the first 4 days of ICU admission than those who did not develop a secondary infection.
authors.affiliation: 1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.
authors.forename: Lonneke A
authors.initials: LA
authors.lastname: van Vught
authors.affiliation: 1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.
authors.forename: Maryse A
authors.initials: MA
authors.lastname: Wiewel
authors.affiliation: 1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.
authors.forename: Arie J
authors.initials: AJ
authors.lastname: Hoogendijk
authors.affiliation: 3 Department of Epidemiology, Julius Centre for Health Sciences and Primary Care.|4 Department of Intensive Care Medicine, and.
authors.forename: Jos F
authors.initials: JF
authors.lastname: Frencken
authors.affiliation: 1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.|5 Department of Clinical Epidemiology and Biostatistics.
authors.forename: Brendon P
authors.initials: BP
authors.lastname: Scicluna
authors.affiliation: 3 Department of Epidemiology, Julius Centre for Health Sciences and Primary Care.|4 Department of Intensive Care Medicine, and.|6 Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Peter M C
authors.initials: PMC
authors.lastname: Klein Klouwenberg
authors.affiliation: 5 Department of Clinical Epidemiology and Biostatistics.
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: 7 Department of Experimental Immunology and Respiratory Medicine.
authors.forename: Rene
authors.initials: R
authors.lastname: Lutter
authors.affiliation: 8 Department of Intensive Care, and.
authors.forename: Janneke
authors.initials: J
authors.lastname: Horn
authors.affiliation: 8 Department of Intensive Care, and.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.affiliation: 3 Department of Epidemiology, Julius Centre for Health Sciences and Primary Care.|6 Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Marc M J
authors.initials: MMJ
authors.lastname: Bonten
authors.affiliation: 4 Department of Intensive Care Medicine, and.
authors.forename: Olaf L
authors.initials: OL
authors.lastname: Cremer
authors.affiliation: 1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.|9 Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D060085:Coinfection / Q000097:blood* / Q000150:complications; D003428:Cross Infection / Q000097:blood* / Q000150:complications; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000150:complications; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers
keywords: ICU-acquired infection; biomarker; host response; intensive care unit; sepsis