Incidence, Risk Factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit After Admission for Sepsis

Abstract

; for the MARS Consortium 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.

Fatores De Risco Às Infecções Relacionadas À Assistência Em Unidades De Terapia Intensiva*

“…Uma das competências desses núcleos é a notificação de eventos adversos em saúde ao Sistema Nacional de Vigilância Sanitária, incluindo as infecções relacionadas à assistência à saúde (15) . O maior porcentual de mortalidade entre pacientes com infecções relacionadas à assistência à saúde pode estar associado ao fato deste grupo acumular maior gravidade sinalizada pelos elevados valores dos índices prognósticos, assim como maior permanência na unidade de terapia intensiva, maior tempo de uso de drogas vasoativas e de ventilação mecânica -achados estes também identificados em outras evidências científicas (16)(17)(18) .…”

Pulmonary Infections in the Elderly Lead to Impaired Neutrophil Targeting, Which Is Improved by Simvastatin

“…This results in a hostile yet immunoparetic systemic environment. Secondary infections are common after sepsis and are associated with immune suppression (10).…”

Thymosin α1-Based Immunomodulatory Therapy for Sepsis: A Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials

“…epsis is a leading cause of death among critically ill patients, which represents a pressing public health crisis and puts an enormous strain on the healthcare system (1). Despite advances in the diagnosis and treatment, mortality remains strikingly high in patients with sepsis, especially those with septic shock.…”