Inflammatory Mediator Profiles Differ in Sepsis Patients With and Without Bacteremia

Abstract

Systemic levels of cytokines are altered during infection and sepsis. This prospective observational study aimed to investigate whether plasma levels of multiple inflammatory mediators differed between sepsis patients with and those without bacteremia during the initial phase of hospitalization. A total of 80 sepsis patients with proven bacterial infection and no immunosuppression were included in the study. Plasma samples were collected within 24 h of hospitalization, and Luminex® analysis was performed on 35 mediators: 16 cytokines, six growth factors, four adhesion molecules, and nine matrix metalloproteases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs). Forty-two patients (52.5%) and 38 (47.5%) patients showed positive and negative blood cultures, respectively. There were significant differences in plasma levels of six soluble mediators between the two “bacteremia” and “non-bacteremia” groups, using Mann–Whitney U test (p < 0.0014): tumor necrosis factor alpha (TNFα), CCL4, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and TIMP-1. Ten soluble mediators also significantly differed in plasma levels between the two groups, with p-values ranging between 0.05 and 0.0014: interleukin (IL)-1ra, IL-10, CCL2, CCL5, CXCL8, CXCL11, hepatocyte growth factor, MMP-8, TIMP-2, and TIMP-4. VCAM-1 showed the most robust results using univariate and multivariate logistic regression. Using unsupervised hierarchical clustering, we found that TNFα, CCL4, E-selectin, VCAM-1, ICAM-1, and TIMP-1 could be used to discriminate between patients with and those without bacteremia. Patients with bacteremia were mainly clustered in two separate groups (two upper clusters, 41/42, 98%), with higher levels of the mediators. One (2%) patient with bacteremia was clustered in the lower cluster, which compromised most of the patients without bacteremia (23/38, 61%) (χ2 test, p < 0.0001). Our study showed that analysis of the plasma inflammatory mediator profile could represent a potential strategy for early identification of patients with bacteremia.

Characteristics and outcomes of bacteremia among ICU-admitted patients with severe sepsis

“…It is well known that the amount and type of cytokines differ in their severity. For example, cytotoxic cytokines, such as tumor necrosis factor-α, are released more frequently in cases of bacteremia 7 . The variety in the production of cytokines that stimulate inflammation may explain the prevalence of septic shock in the bacteremia group.…”

“…However, in-hospital mortality was not significantly different between patients with and without bacteremia in our study. Previous studies have reported various mortality rates in patients with bacteremia [6][7][8]10,15 . The diversity of the study population, setting, and study design may have contributed to the different impacts of bacteremia, which may have been influenced by the proportion of patients with each pathogenic species in each study 5,14 , or evidence of pathogen may have aided in selecting the appropriate antibiotic 16 .…”

“…However, studies investigating the clinical characteristics and outcomes of bacteremia are rarely reported, even though both bacteremia and sepsis are widespread in critically ill patients 4,5 . Moreover, bacteremia and sepsis are not a nested structure but closely interact with each other 6,7 . The clinical characteristics and implications of bacteremia remain unclear among septic patients [8][9][10] .…”

Astroglia in Sepsis Associated Encephalopathy

“…Therefore, sepsis has only two degrees of severity: sepsis itself and septic shock, which complicates the diagnosis of sepsis at the earlier stages (preceding organ failure) and ultimately may increase the severity of the disease [11]. Sometimes sepsis proceeds in a hidden state and remain undiagnosed, despite the presence of systemic inflammatory response syndrome (SIRS) [12]. The SIRS represents a non-specific complex reaction of the organism to severe damage whether it is an infection, mechanical or thermal injury, pancreatitis etc.…”

Damage-associated molecular patterns in trauma

“…In general, SIRS is classically dominated by overwhelming hyperinflammatory processes which are characterized by elevated circulating levels of multiple powerful cellular and humoral proinflammatory mediators. Of those, notably in the experimental and clinical sepsis-associated SIRS, cytokines (e.g., tumor necrosis factor (TNF), interleukin (IL)-1α, IL-1β, and IL-6), chemokines, growth factors, adhesion molecules, gaseous substances, vasoactive peptides, and cell stress markers have been identified and analyzed [33]. After the concept of SIRS was created, a number of publications emerged heralding the efficacy of SIRS in predicting outcomes after trauma [34,35].…”