• Lonneke A van Vught, Maryse A Wiewel, Arie J Hoogendijk, Jos F Frencken, Brendon P Scicluna, Klein Klouwenberg Peter M C PMC 3 Department of Epidemiology, Julius Centre for Health Sciences and Primary Care. , Aeilko H Zwinderman, Rene Lutter, Janneke Horn, Marcus J Schultz, Bonten Marc M J MMJ 3 Department of Epidemiology, Julius Centre for Health Sciences and Primary Care. 6 , Olaf L Cremer, and Tom van der Poll.
• 1 Center for Experimental and Molecular Medicine.
• Am. J. Respir. Crit. Care Med. 2017 Aug 15; 196 (4): 458-470.

RationaleSepsis 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.ObjectivesTo compare systemic proinflammatory host responses in patients with sepsis who acquire a new infection with those who do not.MethodsConsecutive 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.Measurements And Main ResultsOf 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.ConclusionsPatients 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.

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