Reba Umberger1, Carol L Thompson, Ann K Cashion, David Kuhl, Jim Wan, Charles R Yates, Muthiah P Muthiah, Gianfranco Umberto Meduri. 1. Reba Umberger, PhD, RN, CCRN, is an assistant professor at the College of Nursing, The University of Tennessee in Knoxville, and a research associate at the Veterans Affairs Medical Center at Memphis. Her research interests include risk factors for subsequent infections in patients with sepsis including genetic and epigenetic factors, early detection of sepsis, and long term outcomes in survivors of sepsis. She teaches epidemiology, pathophysiology, and quantitative research. Carol L. Thompson, PhD, DNP, RN, is professor of critical care nursing at the University of Kentucky. She was a professor in the College of Nursing, The University of Tennessee Health Science Center, when this research was conducted and chaired the dissertation committee for this research. Her research interests are genetics, dyspnea, pain, and immobility in critically ill adults. Ann K. Cashion, PhD, RN, is scientific director, Division of Intramural Research at the National Institutes of Health/National Institute of Nursing Research. Dr Ann Cashion was a professor and chair, College of Nursing, The University of Tennessee Health Science Center, when this research was conducted. Her primary area of research interests is discovery of genomic biomarkers to predict patient outcomes and guide therapies. David Kuhl, PharmD, is professor of pharmacy at the School of Pharmacy, Union University. Dr Kuhl currently teaches in both basic science and applied pharmacy courses at the School of Pharmacy. His current research primarily involves projects conducted by PGY-1 pharmacy residents affiliated with Union University. Jim Wan, PhD, is associate professor of biostatistics and epidemiology, The University of Tennessee. Dr Wan is an experienced biostatistician collaborating with researchers all over the medical campus. He has been instrumental in various observational studies, clinical trials, and health services research. Charles R. Yates, PharmD, PhD, is professor of pharmaceutical sciences, The Universi
Abstract
BACKGROUND: Health care-associated infections (HAIs) are the target of many well-known preventive measures in the intensive care unit (ICU); however, little is known about post-sepsis-induced immunosuppression. OBJECTIVES: This study explores the relationship between baseline plasma levels of inflammatory cytokines interleukin 6 (IL-6), IL-10, and IL-6:IL-10 and subsequent development of HAIs in patients with admitted with sepsis. METHODS: Prospective observational study was conducted among veterans admitted to the ICU with sepsis and monitored daily through ICU discharge (up to 28 days) to investigate HAI development. Baseline plasma IL-6 and IL-10 levels were measured with a multiplex bead based assay. Exaggerated systemic inflammation was defined as the fourth quartile (IL-6 and IL-10) compared with other quartiles. RESULTS: We recruited 78 patients over 18 months, primarily older (65.5 ± 12.6 years) men (94.9%) with underlying comorbidities (93.9%) and a high severity of illness (Acute Physiologic and Chronic Health Evaluation II score 20.6 ± 6.4). Seventeen patients (21.7%) developed at least 1 HAI, and candidemia was the leading infection. Patients with exaggerated baseline systemic inflammation developed a nonsignificantly higher proportion of HAI as compared with those not developing HAI (IL-6: 31.6% vs 18.6%, P = .55; IL-10: 26.3% vs 20.3%, P = .43). DISCUSSION: Patients with exaggerated systemic inflammation had a higher severity of illness, but not a statistically significant higher incidence of HAI. A larger, more adequately powered sample with serial cytokine measures is needed. Routine surveillance cultures are needed. Health care-associated infection may occur in the absence of fever, and the emerging incidence of Candida is a concern. Immune suppression after sepsis should be recognized as a risk for HAI development. Antibiotic therapy should be targeted with prompt de-escalation of empiric therapy per established guidelines to preserve normal flora.
BACKGROUND: Health care-associated infections (HAIs) are the target of many well-known preventive measures in the intensive care unit (ICU); however, little is known about post-sepsis-induced immunosuppression. OBJECTIVES: This study explores the relationship between baseline plasma levels of inflammatory cytokines interleukin 6 (IL-6), IL-10, and IL-6:IL-10 and subsequent development of HAIs in patients with admitted with sepsis. METHODS: Prospective observational study was conducted among veterans admitted to the ICU with sepsis and monitored daily through ICU discharge (up to 28 days) to investigate HAI development. Baseline plasma IL-6 and IL-10 levels were measured with a multiplex bead based assay. Exaggerated systemic inflammation was defined as the fourth quartile (IL-6 and IL-10) compared with other quartiles. RESULTS: We recruited 78 patients over 18 months, primarily older (65.5 ± 12.6 years) men (94.9%) with underlying comorbidities (93.9%) and a high severity of illness (Acute Physiologic and Chronic Health Evaluation II score 20.6 ± 6.4). Seventeen patients (21.7%) developed at least 1 HAI, and candidemia was the leading infection. Patients with exaggerated baseline systemic inflammation developed a nonsignificantly higher proportion of HAI as compared with those not developing HAI (IL-6: 31.6% vs 18.6%, P = .55; IL-10: 26.3% vs 20.3%, P = .43). DISCUSSION: Patients with exaggerated systemic inflammation had a higher severity of illness, but not a statistically significant higher incidence of HAI. A larger, more adequately powered sample with serial cytokine measures is needed. Routine surveillance cultures are needed. Health care-associated infection may occur in the absence of fever, and the emerging incidence of Candida is a concern. Immune suppression after sepsis should be recognized as a risk for HAI development. Antibiotic therapy should be targeted with prompt de-escalation of empiric therapy per established guidelines to preserve normal flora.