Diagnostic and prognostic value of sCD14-ST—presepsin for patients admitted to hospital intensive care unit (ICU)

Mortality from severe sepsis and septic shock differs across continents, countries, and regions. We aimed to use data from the Surviving Sepsis Campaign (SSC) to compare models of care and outcomes for patients with severe sepsis and septic shock in the USA and Europe. The SSC was introduced into more than 200 sites in Europe and the USA. All patients identified with severe sepsis and septic shock in emergency departments or hospital wards and admitted to intensive care units (ICUs), and those with sepsis in ICUs were entered into the SSC database. Patients entered into the database from its launch in January, 2005, through January, 2010, in units with at least 20 patients and 3 months of enrolment of patients were included in this analysis. Patients included in the cohort were limited to those entered in the first 4 years at every site. We used random-effects logistic regression to estimate the hospital mortality odds ratio (OR) for Europe relative to the USA. We used random-effects linear regression to find the relation between lengths of stay in hospital and ICU and geographic region. 25 375 patients were included in the cohort. The USA included 107 sites with 18 766 (74%) patients, and Europe included 79 hospital sites with 6609 (26%) patients. In the USA, 12 218 (65·1%) were admitted to the ICU from the emergency department whereas in Europe, 3405 (51·5%) were admitted from the wards. The median stay on the hospital wards before ICU admission was longer in Europe than in the USA (1·0 vs 0·1 days, difference 0·9, 95% CI 0·8-0·9). Raw hospital mortality was higher in Europe than in the USA (41·1%vs 28·3%, difference 12·8, 95% CI 11·5-14·7). The median length of stay in ICU (7·8 vs 4·2 days, 3·6, 3·3-3·7) and hospital (22·8 vs 10·5 days, 12·3, 11·9-12·8) was longer in Europe than in the USA. Adjusted mortality in Europe was not significantly higher than that in the USA (32·3%vs 31·3%, 1·0, -1·7 to 3·7, p=0·468). Complete compliance with all applicable elements of the sepsis resuscitation bundle was higher in the USA than in Europe (21·6%vs 18·4%, 3·2, 2·2-4·4). The significant difference in unadjusted mortality and the fact that this difference disappears with severity adjustment raise important questions about the effect of the approach to critical care in Europe compared with that in the USA. The effect of ICU bed availability on outcomes in patients with severe sepsis and septic shock requires further investigation. Copyright © 2012 Elsevier Ltd. All rights reserved.

CD14 is present in macrophage, monocyte, and granulocyte cells and their cell membranes, and it is said to be responsible for intracellular transduction of endotoxin signals. Its soluble fraction is present in blood and is thought to be produced in association with infections. It is called the soluble CD14-subtype (sCD14-ST), and in the following text it is referred to by its generic name, presepsin. We have previously reported that presepsin is produced in association with infection and that it is specifically expressed in sepsis. In the present study we developed a new rapid diagnostic method by using a chemiluminescent enzyme immunoassay that allowed making automated measurements in a shorter time. The results of using this method to measure presepsin values in different pathological conditions were normal, 294.2 ± 121.4 pg/ml; local infection, 721.0 ± 611.3 pg/ml; systemic inflammatory response syndrome, 333.5 ± 130.6 pg/ml; sepsis, 817.9 ± 572.7 pg/ml; and severe sepsis, 1,992.9 ± 1509.2 pg/ml; the presepsin values were significantly higher in patients with local infection, sepsis, and severe sepsis than in patients who did not have infection as a complication. In a comparative study with other diagnostic markers of sepsis based on ROC curves, the area under the curve (AUC) of presepsin was 0.845, and greater than the AUC of procalcitonin (PCT, 0.652), C-reactive protein (CRP, 0.815), or interleukin 6 (IL-6, 0.672). In addition, a significant correlation was found between the APACHE II scores, an index of disease severity, and the presepsin values, suggesting that presepsin values can serve as a parameter that closely reflects the pathology.

The clinical usefulness of presepsin for discriminating between bacterial and nonbacterial infections (including systemic inflammatory response syndrome) was studied and compared with procalcitonin (PCT) and interleukin-6 (IL-6) in a multicenter prospective study. Suspected sepsis patients (n = 207) were enrolled into the study. Presepsin levels in patients with systemic bacterial infection and localized bacterial infection were significantly higher than in those with nonbacterial infections. In addition, presepsin, PCT, and IL-6 levels in patients with bacterial infectious disease were significantly higher than in those with nonbacterial infectious disease (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). The area under the receiver operating characteristic curve was 0.908 for presepsin, 0.905 for PCT, and 0.825 for IL-6 in patients with bacterial infectious disease and those with nonbacterial infectious disease. The cutoff value of presepsin for discrimination of bacterial and nonbacterial infectious diseases was determined to be 600 pg/ml, of which the clinical sensitivity and specificity were 87.8 % and 81.4 %, respectively. Presepsin levels did not differ significantly between patients with gram-positive and gram-negative bacterial infections. The sensitivity of blood culture was 35.4 %; that for presepsin was 91.9 %. Also there were no significant differences in presepsin levels between the blood culture-positive and -negative groups. Consequently, presepsin is useful for the diagnosis of sepsis, and it is superior to conventional markers and blood culture.