Universität zu Köln

van Vught, Lonneke A., Klouwenberg, Peter M. C. Klein, Spitoni, Cristian, Scicluna, Brendon P., Wiewel, Maryse A., Horn, Janneke, Schultz, Marcus J., Nurnberg, Peter, Bonten, Marc J. M., Cremer, Olaf L. and van der Poll, Tom (2016). Incidence, Risk Factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit After Admission for Sepsis. JAMA-J. Am. Med. Assoc., 315 (14). S. 1469 - 1480. CHICAGO: AMER MEDICAL ASSOC. ISSN 1538-3598

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Abstract

IMPORTANCE Sepsis is considered to induce immune suppression, leading to increased susceptibility to secondary infections with associated late mortality. OBJECTIVE To determine the clinical and host genomic characteristics, incidence, and attributable mortality of intensive care unit (ICU)-acquired infections in patients admitted to the ICU with or without sepsis. DESIGN, SETTING, AND PARTICIPANTS Prospective observational study comprising consecutive admissions of more than 48 hours in 2 ICUs in the Netherlands from January 2011 to July 2013 stratified according to admission diagnosis (sepsis or noninfectious). MAIN OUTCOMES AND MEASURES The primary outcome was ICU-acquired infection (onset >48 hours). Attributable mortality risk (fraction of mortality that can be prevented by elimination of the risk factor, acquired infection) was determined using time-to-event models accounting for competing risk. In a subset of sepsis admissions (n = 461), blood gene expression (whole-genome transcriptome in leukocytes) was analyzed at baseline and at onset of ICU-acquired infectious (n = 19) and noninfectious (n = 9) events. RESULTS The primary cohort included 1719 sepsis admissions (1504 patients; median age, 62 years; interquartile range [IQR], 51-71 years]; 924 men [61.4%]). A comparative cohort included 1921 admissions (1825 patients, median age, 62 years; IQR, 49-71 years; 1128 men [61.8%] in whom infection was not present in the first 48 hours. Intensive care unit-acquired infections occurred in 13.5% of sepsis ICU admissions (n = 232) and 15.1% of nonsepsis ICU admissions (n = 291). Patients with sepsis who developed an ICU-acquired infection had higher disease severity scores on admission than patients with sepsis who did not develop an ICU-acquired infection (Acute Physiology and Chronic Health Evaluation IV [APACHE IV] median score, 90 [ IQR, 72-107] vs 79 [ IQR, 62-98]; P < .001) and throughout their ICU stay but did not have differences in baseline gene expression. The population attributable mortality fraction of ICU-acquired infections in patients with sepsis was 10.9% (95% CI, 0.9%-20.6%) by day 60; the estimated difference between mortality in all patients with a sepsis admission diagnosis and mortality in those without ICU-acquired infection was 2.0% (95% CI, 0.2%-3.8%; P = .03) by day 60. Among nonsepsis ICU admissions, ICU-acquired infections had a population attributable mortality fraction of 21.1% (95% CI, 0.6%-41.7%) by day 60. Compared with baseline, blood gene expression at the onset of ICU-acquired infections showed reduced expression of genes involved in gluconeogenesis and glycolysis. CONCLUSIONS AND RELEVANCE Intensive care unit-acquired infections occurred more commonly in patients with sepsis with higher disease severity, but such infections contributed only modestly to overall mortality. The genomic response of patients with sepsis was consistent with immune suppression at the onset of secondary infection.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code van Vught, Lonneke A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klouwenberg, Peter M. C. Klein UNSPECIFIED UNSPECIFIED UNSPECIFIED Spitoni, Cristian UNSPECIFIED UNSPECIFIED UNSPECIFIED Scicluna, Brendon P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiewel, Maryse A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Horn, Janneke UNSPECIFIED UNSPECIFIED UNSPECIFIED Schultz, Marcus J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nurnberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bonten, Marc J. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cremer, Olaf L. UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Poll, Tom UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-278738
DOI:	10.1001/jama.2016.2691
Journal or Publication Title:	JAMA-J. Am. Med. Assoc.
Volume:	315
Number:	14
Page Range:	S. 1469 - 1480
Date:	2016
Publisher:	AMER MEDICAL ASSOC
Place of Publication:	CHICAGO
ISSN:	1538-3598
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NOSOCOMIAL INFECTIONS; SEPTIC SHOCK; IMMUNOSUPPRESSION; DEFINITIONS; DECONTAMINATION; INFLAMMATION; OROPHARYNX; PARADIGM; MODELS; TRACT Multiple languages Medicine, General & Internal Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27873