The diagnostic value of procalcitonin (PCT) for patients with autoimmune diseases (AID) remains controversial and few studies focused on ICU patients. We sought to determine its diagnostic and prognostic values in this clowd.
A prospective observational study was conducted in AID patients admitted to the ICU. Serum PCT levels were measured on ICU admission and subsequently at days 1, 3, 5 and 7, and peak PCT levels within 24 h (PCTpeak) were analyzed the utility for bacterial infection. The relationship of PCTpeak and SOFA score and severity of sepsis was performed correlation analysis. The change of PCT over time reflected as PCT clearance was compared to ICU 28-day mortality.
One hundred twelve patients were divided into bacterial infection group (group I, n = 54) and nonbacterial condition group (group II, n = 58). The median PCTpeak (range, μg/L) was higher in the group I than that in the group II (1.95 [0.38–37.56] vs. 0.64 [0.05–7.83], p = 0.002). PCTpeak had the best single predictor of bacterial infection (area under the curve [AUC], 0.902, p < 0.001) with a sensitivity of 79.6 % and a specificity of 89.6 % at the threshold of 0.94 μg/L. PCTpeak was also positive correlation with severity of sepsis (r = 0.731, p = 0.002), but its correlation with SOFA score was only found in subjects with bacterial infection (r = 0.798, p < 0.001). Importantly, the 5-day PCT clearance (PCTc-d5), rather than absolute PCT values, could earlier discriminate survivors (n = 73) from nonsurvivors (n = 39) (68.8 ± 9.8 vs. 21.8 ± 17.5 %, p < 0.001, respectively). PCTc-d5 < 50 % was an independent predictor of mortality (odds ratio 5.1, 95 % confidence interval 3.5 to 7.5; p = 0.001).
In critically ill patients with AID, elevated PCT levels are valuable for bacterial infection and are significantly positive correlation with the septic severity. Five-day PCT clearance may provide independent prognostic information. Larger, prospective trials are warranted to confirm the benefit.
Electronic supplementary material
The online version of this article (doi:10.1186/s12871-015-0122-9) contains supplementary material, which is available to authorized users.
Procalcitonin; Procalcitonin clearance; Autoimmune diseases; Critically ill patients; Bacterial infection; Outcome
Objective: Sepsis is a life-threatening disease which is associated with high rates of morbidity and mortality. The critically ill patients often manifest a Systemic Inflammatory Response Syndrome (SIRS) which is independent of an infection. The early diagnosis of different severities of sepsis is important for an early implementation of the specific therapies. Our objective was to evaluate the diagnostic and the prognostic values of blood Procalcitonin (PCT) in cases of bacterial septicaemia in children.
Methods: The total sample comprised of 150 subjects who were admitted to the ICU with septicaemia and 50 normal, healthy, age and sex matched children. The first sample was collected at the time of admission, before the start of the antibiotic therapy (T0). A second sample was collected at 24 hours (T24) and a final sample was collected at 96 hours (T96). A PCT value of > 0.5ng/ml was accepted as positive.
Results: 63% of the children who were diagnosed with a bacterial aetiology showed detectable blood PCT levels with higher concentrations, while in the children who were diagnosed with a viral aetiology, only 22.2 % had detectable PCT levels, but in lower concentrations. The mean percentage reduction in the PCT value among the bacterial infection subjects was 44.39 ± 41.82 as compared to that in the viral infection subjects (5.71 ± 26.68) and in the subjects where the aetiology was not established (5.71 ± 26.68).
Conclusion: The results which were obtained in our study con- firmed that the PCT levels were a better marker for the bacterial infections. The PCT measurements may be used as a guide to the antibiotic therapy in critically ill children with suspected sepsis.
Procalcitonin; Sepsis; SIRS; Bacterial infection
We investigated the diagnostic and prognostic utilities of procalcitonin (PCT), B-type natriuretic peptide (BNP), and neutrophil gelatinase-associated lipocalin (NGAL) in critically ill patients with suspected sepsis, for whom sepsis was diagnosed clinically or based on PCT concentrations.
PCT, BNP, and NGAL concentrations were measured in 340 patients and were followed up in 109 patients. All studied biomarkers were analyzed according to the diagnosis, severity, and clinical outcomes of sepsis.
Clinical sepsis and PCT-based sepsis showed poor agreement (kappa = 0.2475). BNP and NGAL showed significant differences between the two groups of PCT-based sepsis (P = 0.0001 and P < 0.0001), although there was no difference between the two groups of clinical sepsis. BNP and NGAL were significantly different according to the PCT staging and sepsis-related organ failure assessment subscores (P < 0.0001, all). BNP and PCT concentrations were significantly higher in the non-survivors than in the survivors (P = 0.0002) and showed an equal ability to predict in-hospital mortality (P = 0.0001). In the survivors, the follow-up NGAL and PCT concentrations were significantly lower than the initial values (148.7 ng/mL vs. 214.5 ng/mL, P < 0.0001; 0.61 ng/mL vs. 5.56 ng/mL, P = 0.0012).
PCT-based sepsis diagnosis seems to be more reliable and discriminating than clinical sepsis diagnosis. Multimarker approach using PCT, BNP, and NGAL would be useful for the diagnosis, staging, and prognosis prediction in the critically ill patients with suspected sepsis.
B-type natriuretic peptide; Neutrophil gelatinase-associated lipocalin; Procalcitonin; Sepsis; Diagnosis; Prognosis
Procalcitonin (PCT) is a reliable biomarker of sepsis and infection. The level of PCT associated with sepsis and infection in patients with traumatic brain injury is currently unknown. The purpose of this study was to investigate the value of PCT and C-reactive protein (CRP) as diagnostic markers of sepsis and to evaluate the prognostic value of these markers related to the severity of injury, sepsis and mortality.
105 adult patients with neurotrauma were enrolled in this study from June 2011 to February 2013. PCT and CRP were measured at admission and 2, 3, 5 and 7 days after admission. The sepsis criteria established by American College of Chest Physicians /Society of Critical Care Medicine Consensus Conference were used to identify patients. Injury Severity Score (ISS) and Glasgow Coma Score (GCS) were used to assess the severity of the injury. All these patients were monitored for 28 days.
At admission, the median level of PCT was consistent with the severity of brain injury as follows: mild 0.08 ng/ml (0.05 - 0.13), moderate 0.25 ng/ml (0.11 - 0.55) and severe 0.31 ng/ml (0.17 - 0.79), but the range of CRP levels varied greatly within the given severity of brain injury. Seventy-one (67.6%) patients developed sepsis. The initial levels of PCT at admission were statistically higher in patients with sepsis, compared with patients with systemic inflammatory response syndrome (SIRS), but there were no differences in the initial concentration of CRP between sepsis and SIRS. After adjusting for these parameters, multivariate logistic regression analysis revealed that PCT was an independent risk factor for septic complications (p < 0.05). The areas under the ROCs at admission for the prediction of mortality were 0.76 (p < 0.05) and 0.733 for PCT and CRP, respectively.
Increased levels of PCT during the course of the ICU stay could be an important indicator for the early diagnosis of sepsis after neurotrauma. In addition, high serum levels of PCT in patients with neurotrauma at admission indicate an increased risk of septic complications, and the daily measurement of PCT assists in guiding antibiotic therapy in neurotrauma patients.
Procalcitonin; Systemic inflammatory response syndrome (SIRS); Sepsis; Mortality; Traumatic brain injury
Serum procalcitonin (PCT) levels may have predictive value in the prognosis of postoperative sepsis in elderly patients who have undergone colorectal surgery for colorectal cancer in intensive care units (ICUs). A prospective study involving 90 critically ill patients who underwent colorectal surgery for colorectal cancer in ICUs was performed. Twenty-eight patients were diagnosed with sepsis, in accordance with the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria, and these patients were included in the sepsis group. Sixty-two patients, who were without evidence of sepsis, were enrolled in the control group. We measured the serum PCT concentrations preoperatively (immediately before induction of anesthesia), upon arrival in the ICU (ICU day 0), on the morning of the first postoperative day (postoperative day 1), and on the morning of the third postoperative day (postoperative day 3). The C-reactive protein (CRP) index, acute physiology and chronic health evaluation II (APACHE II) score, mechanical duration of ventilation, mortality rate, incidence of multiple organ failure, and usage of continuous renal replacement therapy were evaluated. The area under the curve for the receiver operating characteristic curve (AUC-ROCC) was measured to explore the association between the serum PCT and the prognosis. In the sepsis group, 12/28 patients died (mortality rate 43 %). In the control group, 6/62 patients died (mortality rate 9.7 %). On the first postoperative day, the serum PCT level was dramatically higher in the sepsis group than in the control group (2.71 ± 1.13 vs. 1.37 ± 0.57, P ≤ 0.05). The PCT level on the first postoperative day was distinctly higher than that measured upon arrival in the ICU (2.71 ± 1.13 vs. 1.31 ± 0.58, P ≤ 0.05). In the two groups, the CRP concentrations were both markedly higher on the first postoperative day than upon arrival in the ICU (138.89 ± 45.12 vs. 70.43 ± 23.54 in the sepsis group, and 133.13 ± 44.91 vs. 69.65 ± 24.98 in the control group, P ≤ 0.05). Linear regression analysis was performed. The results suggest that the PCT and APACHE-II scores were not significantly associated. On the first and third postoperative days, the PCT levels were associated with increased odds of sepsis (AUC-ROCC, 95 % confidence interval 0.817–0.973, P = 0.000, and 0.755–0.944, P = 0.000, respectively). The outcomes of patients in the sepsis group were worse than those in the control group. PCT levels appear to be early markers of postoperative sepsis in elderly patients undergoing colorectal surgery for colorectal cancer during the ICU course. These findings could allow for early identification of postoperative septic complications and be used for prognostic evaluation of these patients.
Elderly patients; Sepsis; Emergency colorectal surgery; Procalcitonin; Prognosis
A continued need exists for effective diagnostic biomarkers in bacterial sepsis among critically ill patients, despite increasing use of available biomarkers such as procalcitonin (PCT). Interleukin-27 (IL-27) has shown early promise in a recent preliminary study, exhibiting high specificity and positive predictive values for bacterial infection in critically ill children. This validation study was performed to assess the value of IL-27 in predicting bacterial infection among patients admitted to the pediatric intensive care unit and to compare its performance with that of PCT.
A single-center (n = 702) prospective study was performed comparing both IL-27 and PCT levels between bacterially infected and uninfected cohorts in the pediatric intensive care unit. Infected status was determined by a chart review by an intensivist blinded to biomarker results. Formal performance comparisons included calculations of receiver operating characteristic (ROC) curves for IL-27 and PCT individually in addition to a combination strategy using a decision tree generated by classification and regression tree (CART) methodology. Secondary analysis focusing on subjects with documented bloodstream infections was performed.
The overall infection rate was 27 %. ROC curves for the primary analysis yielded areas under the curve (AUCs) of 0.64 (0.59 to 0.68) for IL-27 and 0.61 (0.56 to 0.65) for PCT. Secondary analysis defining infected status exclusively through positive blood cultures yielded AUCs of 0.75 (0.68 to 0.81) for IL-27 and 0.64 (0.57 to 0.71) for PCT, with a specificity of 95 % (92 % to 97 %) for the prior established IL-27 cut-point value of at least 5.0 ng/ml. Similar AUCs were found for the subset of immunocompromised patients. In a CART-derived analysis taking immunocompromised status into consideration, a combination of IL-27 and PCT yielded an AUC of 0.81 (0.75 to 0.86), statistically improved from either IL-27 or PCT alone.
Despite having a modest predictive value for infection independent of source, IL-27 may serve as a useful biomarker in estimating risk of bacterial infection among critically ill pediatric patients with bloodstream infections. In particular, among immunocompromised subjects, this diagnostic biomarker may be helpful either alone or using a combination strategy with other available biomarkers.
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Background—Infection of pancreatic necrosis has a
major impact on clinical course, management, and outcome in acute
pancreatitis. Currently, guided fine needle aspiration is the only
means for an early and accurate diagnosis of infected necrosis.
Procalcitonin (PCT), a 116 amino acid propeptide of calcitonin, and
interleukin 8 (IL-8), a strong neutrophil activating cytokine, are
markers of severe inflammation and sepsis.
Aims—To analyse the clinical value of PCT and
IL-8 as biochemical parameters for predicting infected necrosis in
Patients and methods—Fifty patients with acute
pancreatitis entered this prospective study and were stratified into
three groups according to morphological and bacteriological findings: 18 patients with oedematous pancreatitis (group I), 14 patients with
sterile necrosis (group II), and 18 patients who developed infected
necrosis a median of 13.5 days after the onset of symptoms (group III).
After admission serum samples were drawn daily for two weeks.
Concentrations of PCT and IL-8 were measured by chemoluminescent immunoassays (upper reference range 0.5 ng/ml for PCT and 70 pg/ml for IL-8). The routine parameter C-reactive protein was determined by
laser nephelometry (upper reference range 10 mg/l).
Results—Median concentrations of PCT and IL-8
were significantly higher in patients with infected necrosis than in
those with sterile necrosis during the observation period, whereas
there was no difference in C-reactive protein. In oedematous
pancreatitis overall median concentrations of all three parameters were
low. By receiver operating characteristics best cut off levels for predicting infected necrosis or persisting pancreatic sepsis were 1.8 ng/ml for PCT and 112 pg/ml for IL-8. If these cut off levels were reached on at least two days, sensitivity, specificity, and accuracy for the prediction of infected necrosis were 94%, 91%, and
92% for PCT and 72%, 75%, and 74% for IL-8, respectively. After
surgical treatment of infected necrosis median PCT and IL-8 values
continued to be significantly higher in patients with persisting pancreatic sepsis (n=11) compared with those having an uneventful postoperative course (n=7). For the preoperative differentiation between infected necrosis and sterile necrosis guided fine needle aspiration was performed in 24 patients with necrotising pancreatitis and reached a diagnostic accuracy of 84% compared with 87% for PCT,
and 68% for IL-8. There was no correlation between the aetiology of
acute pancreatitis or the extent of necrosis and PCT or IL-8.
Conclusion—PCT and IL-8 are found in high
concentrations in infected necrosis and associated systemic
complications in patients with acute pancreatitis. The course of PCT
shows the closest correlation with the presence of infected necrosis.
Monitoring of serum PCT is a potential new marker for the non-invasive
and accurate prediction of infected necrosis as well as for the
selection of patients with persisting septic complications after
procalcitonin; interleukin 8; infected necrosis; acute pancreatitis
Procalcitonin (PCT) has emerged as a valuable marker of sepsis. The potential role of PCT in diagnosis and therapy monitoring of intravascular catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) is still unclear and was evaluated.
Forty-six patients were included in the study, provided they were free of infection upon admission and presented the first episode of suspected CRBSI during their ICU stay. Patients who had developed any other infection were excluded. PCT was measured daily during the ICU hospitalization. Primary endpoint was proven CRBSI. Therapy monitoring as according to infection control was also evaluated.
Among the 46 patients, 26 were diagnosed with CRBSI. Median PCT on the day of infection suspicion (D0) was 7.70 and 0.10 ng/ml for patients with and without proven CRBSI, respectively (p < 0.001). The area under the curve (AUC) for PCT was 0.990 (95% CI; 0.972 – 1.000), whereas a cut-off value of 0.70 ng/ml provided sensitivity and specificity of 92.3 and 100% respectively. In contrast, the AUC for white blood cells (WBC) was 0.539 (95% CI; 0.369 – 0.709), and for C-reactive protein (CRP), 0.603 (95% CI; 0.438 – 0.768). PCT was the best predictor of proven infection. Moreover, an increase >0.20 ng/ml of PCT between the D0 and any of the 4 preceding days was associated with a positive predictive value exceeding 96%. PCT concentrations from the D2 to D6 after suspected infection tended to decrease in controlled patients, whereas remained stable in non-controlled subjects. A PCT concentration exceeding 1.5 ng/ml during D3 was associated with lack of responsiveness to therapy (p = 0.028).
We suggest that PCT could be a helpful diagnostic and prognostic marker of CRBSI in critically ill patients. Both absolute values and variations should be considered.
The aims of this study were to assess the reliability of circulating cell-free DNA (cf-DNA) concentrations, compared with C-reactive protein (CRP), procalcitonin (PCT) and eosinophil count, in the diagnosis of infections in patients with systemic inflammatory response syndrome (SIRS) and their prognostic values in a cohort of critically ill patients.
We conducted a prospective cohort study in a medical-surgical intensive care unit of a university hospital. Eosinophil count and concentrations of cf-DNA, CRP, and PCT were measured in patients who fulfilled SIRS criteria at admission to the intensive care unit (ICU) and a second determination 24 hours later. DNA levels were determined by a PCR method using primers for the human beta-haemoglobin gene.
One hundred and sixty consecutive patients were included: 43 SIRS without sepsis and 117 with sepsis. Levels of CRP and PCT, but not cf-DNA or eosinophil count, were significantly higher in patients with sepsis than in SIRS-no sepsis group on days 1 and 2. PCT on day 1 achieves the best area under the curve (AUC) for sepsis diagnosis (0.87; 95% confidence interval = 0.81-0.94). Levels of cf-DNA do not predict outcome and the accuracy of these biomarkers for mortality prediction was lower than that shown by APACHE II score. PCT decreases significantly from day 1 to day 2 in survivors in the entire cohort and in patients with sepsis without significant changes in the other biomarkers.
Our data do not support the clinical utility of cf-DNA measurement in critical care patients with SIRS. PCT is of value especially for infection identification in patients with SIRS at admission to the ICU.
Both C-reactive protein (CRP) and procalcitonin (PCT) are accepted sepsis markers. However, there is still some debate concerning the correlation between their serum concentrations and sepsis severity. We hypothesised that PCT and CRP concentrations are different in patients with infection or with no infection at a similar severity of organ dysfunction or of systemic inflammatory response.
Patients and methods
One hundred and fifty adult intensive care unit patients were observed consecutively over a period of 10 days. PCT, CRP and infection parameters were compared among the following groups: no systemic inflammatory response syndrome (SIRS) (n = 15), SIRS (n = 15), sepsis/SS (n = 71) (including sepsis, severe sepsis and septic shock [n = 34, n = 22 and n = 15]), and trauma patients (n = 49, no infection).
PCT and CRP concentrations were higher in patients in whom infection was diagnosed at comparable levels of organ dysfunction (infected patients, regression of median [ng/ml] PCT = -0.848 + 1.526 sequential organ failure assessment [SOFA] score, median [mg/l] CRP = 105.58 + 0.72 SOFA score; non-infected patients, PCT = 0.27 + 0.02 SOFA score, P < 0.0001; CRP = 84.53 - 0.19 SOFA score, P < 0.005), although correlation with the SOFA score was weak (R = 0.254, P < 0.001 for PCT, and R = 0.292, P < 0.001 for CRP). CRP levels were near their maximum already during lower SOFA scores, whereas maximum PCT concentrations were found at higher score levels (SOFA score > 12).
PCT and CRP concentrations were 1.58 ng/ml and 150 mg/l in patients with sepsis, 0.38 ng/ml and 51 mg/l in the SIRS patients (P < 0.05, Mann–Whitney U-test), and 0.14 ng/ml and 72 mg/l in the patients with no SIRS (P < 0.05). The kinetics of both parameters were also different, and PCT concentrations reacted more quickly than CRP.
PCT and CRP levels are related to the severity of organ dysfunction, but concentrations are still higher during infection. Different sensitivities and kinetics indicate a different clinical use for both parameters.
calcitonin; C-reactive protein; infection; procalcitonin; sepsis; sequential organ failure assessment score; systemic inflammatory response syndrome
High-mobility group box-1 protein (HMGB1) has been known as a chromosomal protein for many years. HMGB1 has recently been shown to be a proinflammatory cytokine with a role in the immunopathogenesis of sepsis. Lipopolysaccharide-binding protein (LBP) has a central role in the innate immune response when the host is challenged by bacterial pathogens. Procalcitonin (PCT) has been suggested as a marker of severe bacterial infections and sepsis. The aim of the present study was to investigate levels of HMGB1, LBP and PCT in a well-characterised sepsis cohort. The study plan included analysis of the levels of the inflammatory markers in relation to the severity of infection, to the prognosis and to the ability to identify patients with bacteraemia.
Patients suspected of having severe infections and admitted to a department of internal medicine were included in a prospective manner. Demographic data, comorbidity, routine biochemistry, microbiological data, infection focus, severity score and mortality on day 28 were recorded. Plasma and serum were sampled within 24 hours after admission. Levels of all studied markers (HMGB1, LBP, PCT, IL-6, C-reactive protein, white blood cell count and neutrophils) were measured with commercially available laboratory techniques.
A total of 185 adult patients were included in the study; 154 patients fulfilled our definition of infection. Levels of HMGB1, LBP and PCT were higher in infected patients compared with a healthy control group (P < 0.0001). Levels of HMGB1, LBP and PCT were higher in the severe sepsis group compared with the sepsis group (P < 0.01). No differences were observed in levels of the inflammatory markers in fatal cases compared with survivors. Levels of all studied markers were higher in bacteraemic patients compared with nonbacteraemic patients (P < 0.05). PCT performed best in a receiver–operator curve analysis discriminating between bacteraemic and nonbacteraemic patients (P < 0.05). HMGB1 correlated to LBP, IL-6, C-reactive protein, white blood cell count and neutrophils (P < 0.001). LBP correlated to PCT, IL-6 and C-reactive protein (P < 0.001).
Levels of HMGB1, PCT and LBP were higher in infected patients compared with those in healthy controls, and levels were higher in severe sepsis patients compared with those in sepsis patients. Levels of all studied inflammatory markers (HMGB1, LBP, PCT, IL-6) and infection markers (C-reactive protein, white blood cell count, neutrophils) were elevated among bacteraemic patients. PCT performed best as a diagnostic test marker for bacteraemia.
We studied the usefulness of serum procalcitonin (PCT), interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) levels and C-reactive protein (CRP) levels, in differentiating between systemic inflammatory response syndrome (SIRS) and sepsis in critically ill patients. Methods. In this single centre prospective observational study we included all consecutive patients admitted with SIRS or sepsis to the ICU. Blood samples for measuring CRP, PCT, IL-6 and LBP were taken every day until ICU discharge. Results. A total of 76 patients were included, 32 with sepsis and 44 with SIRS. Patients with sepsis were sicker on admission and had a higher mortality. CRP, PCT, IL-6 and LBP levels were significantly higher in patients with sepsis as compared to SIRS. With PCT levels in the first 24 hours after ICU admission <2 ng/mL, sepsis was virtually excluded (negative predictive value 97%). With PCT >10 ng/mL, sepsis with bacterial infection was very likely (positive predictive value 88%). PCT was best at discriminating between SIRS and sepsis with the highest area under the ROC curve (0.95, 95% CI 0.90–0.99). Discussion. This study showed that PCT is more useful than LBP, CRP and IL-6 in differentiating sepsis from SIRS.
Sepsis, severe sepsis and septic shock are common conditions with high mortality. Their early diagnosis in the Emergency Department (ED) is one of the keys to improving survival. Procalcitonin (PCT) has been used as a biomarker in septic patients but has limited specificity and can be elevated in other scenarios of systemic inflammatory response syndrome (SIRS). Soluble CD14 (sCD14) or presepsin is the free fragment of a glycoprotein expressed on monocytes and macrophages. Preliminary reports suggest that levels of presepsin are significantly higher in septic patients than in healthy individuals. The aim of this study is to investigate the diagnostic and prognostic value of presepsin compared to PCT in people presenting at the ED with SIRS and suspected sepsis or septic shock.
This study was conducted in two major hospitals in Turin, Italy. One hundred six patients presenting to the EDs with suspected sepsis or septic shock were included, and another eighty-three patients affected by SIRS, but with no clinical evidence of infection, were recruited as controls. Blood samples were collected at first medical evaluation and for some patients after 24 and 72 h. The samples were analyzed using the PATHFAST Presepsin assay for sCD14, and commercial kits were used for other determinations (for example, PCT). Definitive diagnosis and survival rates were obtained afterward by analysis of digital medical records.
Elevated concentrations of presepsin at presentation were observed in septic patients compared to control patients. The same trend was observed for mean values of PCT. Higher values of presepsin were observed in septic patients at presentation (time 0). The diagnostic accuracy of PCT was generally higher, and areas under the curve (AUCs) were 0.875 for PCT and 0.701 for presepsin. Mean presepsin values were significantly higher in nonsurvivor septic patients (60-day mortality) than in survivors. No significant correlation was noted between PCT and survival.
In our experience, presepsin was useful in the early diagnosis of infection in a complex population of patients with SIRS, sepsis, severe sepsis and septic shock who presented to the ED. Presepsin showed a significant prognostic value, and initial values were significantly correlated with in-hospital mortality of patients affected by sepsis, severe sepsis or septic shock.
Procalcitonin (PCT) has been proposed as a diagnostic and prognostic sepsis marker, but has never been validated in febrile patients with prolonged ICU stay.
Patients were included in the study provided they were hospitalised in the ICU for > 10 days, were free of infection and presented a new episode of SIRS, with fever >38°C being obligatory. Fifty patients fulfilled the above criteria. PCT was measured daily during the ICU stay. The primary outcome was proven infection.
Twenty-seven out of 50 patients were diagnosed with infection. Median PCT on the day of fever was 1.18 and 0.17 ng/ml for patients with and without proven infections (p < 0.001). The area under the curve for PCT was 0.85 (95% CI; 0.71-0.93), for CRP 0.65 (0.46-0.78) and for WBC 0.68 (0.49-0.81). A PCT level of 1 ng/mL yielded a negative predictive value of 72% for the presence of infection, while a PCT of 1.16 had a specificity of 100%. A two-fold increase of PCT between fever onset and the previous day was associated with proven infection (p 0.001) (OR = 8.55; 2.4-31.1), whereas a four-fold increase of PCT of any of the 6 preceding days was associated with a positive predictive value exceeding 69.65%. A PCT value less than 0.5 ng/ml on the third day after the advent of fever was associated with favorable survival (p 0.01).
The reported data support that serial serum PCT may be a valuable diagnostic and prognostic marker in febrile chronic critically ill patients.
Sepsis is a major cause of mortality and morbidity in critically ill patients. Procalcitonin (PCT) and C-reactive protein (CRP) are the most frequently used biomarkers in sepsis. We investigated changes in PCT and CRP concentrations in critically ill patients with sepsis to determine which biochemical marker better predicts outcome. We retrospectively analyzed 171 episodes in 157 patients with severe sepsis and septic shock who were admitted to the Samsung Medical Center intensive care unit from March 2013 to February 2014. The primary endpoint was patient outcome within 7 days from ICU admission (treatment failure). The secondary endpoint was 28-day mortality. Severe sepsis was observed in 42 (25%) episodes from 41 patients, and septic shock was observed in 129 (75%) episodes from 120 patients. Fifty-five (32%) episodes from 42 patients had clinically-documented infection, and 116 (68%) episodes from 99 patients had microbiologically-documented infection. Initial peak PCT and CRP levels were not associated with treatment failure and 28-day mortality. However, PCT clearance (PCTc) and CRP (CRPc) clearance were significantly associated with treatment failure (p = 0.027 and p = 0.030, respectively) and marginally significant with 28-day mortality (p = 0.064 and p = 0.062, respectively). The AUC for prediction of treatment success was 0.71 (95% CI, 0.61–0.82) for PCTc and 0.71 (95% CI, 0.61–0.81) for CRPc. The AUC for survival prediction was 0.77 (95% CI, 0.66–0.88) for PCTc and 0.77 (95% CI, 0.67–0.88) for CRPc. Changes in PCT and CRP concentrations were associated with outcomes of critically ill septic patients. CRP may not be inferior to PCT in predicting outcome in these patients.
The management of bloodstream infections especially sepsis is a difficult task. An optimal antibiotic therapy (ABX) is paramount for success. Procalcitonin (PCT) is a well investigated biomarker that allows close monitoring of the infection and management of ABX. It has proven to be a cost-efficient diagnostic tool. In Diagnoses Related Groups (DRG) based reimbursement systems, hospitals get only a fixed amount of money for certain treatments. Thus it's very important to obtain an optimal balance of clinical treatment and resource consumption namely the length of stay in hospital and especially in the Intensive Care Unit (ICU). We investigated which economic effects an optimized PCT-based algorithm for antibiotic management could have.
Materials and methods
We collected inpatient episode data from 16 hospitals. These data contain administrative and clinical information such as length of stay, days in the ICU or diagnoses and procedures. From various RCTs and reviews there are different algorithms for the use of PCT to manage ABX published. Moreover RCTs and meta-analyses have proven possible savings in days of ABX (ABD) and length of stay in ICU (ICUD). As the meta-analyses use studies on different patient populations (pneumonia, sepsis, other bacterial infections), we undertook a short meta-analyses of 6 relevant studies investigating in sepsis or ventilator associated pneumonia (VAP). From this analyses we obtained savings in ABD and ICUD by calculating the weighted mean differences. Then we designed a new PCT-based algorithm using results from two very recent reviews. The algorithm contains evidence from several studies. From the patient data we calculated cost estimates using German National standard costing information for the German G-DRG system.
We developed a simulation model where the possible savings and the extra costs for (in average) 8 PCT tests due to our algorithm were brought into equation.
We calculated ABD savings of -4 days and ICUD reductions of -1.8 days. our algorithm contains recommendations for ABX onset (PCT ≥ 0.5 ng/ml), validation whether ABX is appropriate or not (Delta from day 2 to day 3 ≥ 30% indicates inappropriate ABX) and recommendations for discontinuing ABX (PCT ≤ 0.25 ng/ml).
We received 278, 264 episode datasets where we identified by computer-based selection 3, 263 cases with sepsis. After excluding cases with length of stay (LOS) too short to achieve the intended savings, we ended with 1, 312 cases with ICUD and 268 cases without ICUD. Average length of stay of ICU-patients was 27.7 ± 25.7 days and for Non-ICU patients 17.5 ± 14.6 days respectively. ICU patients had an average of 8.8 ± 8.7 ICUD.
After applying the simulation model on this population we calculated possible savings of € -1, 163, 000 for ICU-patients and € -36, 512 for Non-ICU patients.
Our findings concerning the savings from the reduction of ABD are consistent with other publications. Savings ICUD had never been economically evaluated so far. our algorithm is able to possibly set a new standard in PCT-based ABX. However the findings are based on data modelling. The algorithm will be implemented in 5-10 hospitals in 2012 and effects in clinical reality measured 6 months after implementation.
Managing sepsis with daily monitoring of PCT using our refined algorithm is suitable to save substantial costs in hospitals. Implementation in clinical routine settings will show how much of the calculated effect will be achieved in reality.
Sepsis, a leading cause of death in critically ill patients, is the result of complex interactions between the infecting microorganisms and the host responses that influence clinical outcomes. We evaluated the prognostic value of presepsin (sCD14-ST), a novel biomarker of bacterial infection, and compared it with procalcitonin (PCT).
This is a retrospective, case–control study of a multicenter, randomized clinical trial enrolling patients with severe sepsis or septic shock in ICUs in Italy. We selected 50 survivors and 50 non-survivors at ICU discharge, matched for age, sex and time from sepsis diagnosis to enrollment. Plasma samples were collected 1, 2 and 7 days after enrollment to assay presepsin and PCT. Outcome was assessed 28 and 90 days after enrollment.
Early presepsin (day 1) was higher in decedents (2,269 pg/ml, median (Q1 to Q3), 1,171 to 4,300 pg/ml) than in survivors (1,184 pg/ml (median, 875 to 2,113); P = 0.002), whereas PCT was not different (18.5 μg/L (median 3.4 to 45.2) and 10.8 μg/L (2.7 to 41.9); P = 0.31). The evolution of presepsin levels over time was significantly different in survivors compared to decedents (P for time-survival interaction = 0.03), whereas PCT decreased similarly in the two groups (P = 0.13). Presepsin was the only variable independently associated with ICU and 28-day mortality in Cox models adjusted for clinical characteristics. It showed better prognostic accuracy than PCT in the range of Sequential Organ Failure Assessment score (area under the curve (AUC) from 0.64 to 0.75 vs. AUC 0.53 to 0.65).
In this multicenter clinical trial, we provide the first evidence that presepsin measurements may have useful prognostic information for patients with severe sepsis or septic shock. These preliminary findings suggest that presepsin may be of clinical importance for early risk stratification.
Introduction. Serum procalcitonin (PCT) diagnosed sepsis in critically ill patients; however, its prediction for survival is not well established. We evaluated the prognostic value of dynamic changes of PCT in sepsis patients. Methods. A prospective observational study was conducted in adult ICU. Patients with systemic inflammatory response syndrome (SIRS) were recruited. Daily PCT were measured for 3 days. 48 h PCT clearance (PCTc-48) was defined as percentage of baseline PCT minus 48 h PCT over baseline PCT. Results. 95 SIRS patients were enrolled (67 sepsis and 28 noninfectious SIRS). 40% patients in the sepsis group died in hospital. Day 1-PCT was associated with diagnosis of sepsis (AUC 0.65 (95% CI, 0.55 to 0.76)) but was not predictive of mortality. In sepsis patients, PCTc-48 was associated with prediction of survival (AUC 0.69 (95% CI, 0.53 to 0.84)). Patients with PCTc-48 > 30% were independently associated with survival (HR 2.90 (95% CI 1.22 to 6.90)). Conclusions. PCTc-48 is associated with prediction of survival in critically ill patients with sepsis. This could assist clinicians in risk stratification; however, the small sample size, and a single-centre study, may limit the generalisability of the finding. This would benefit from replication in future multicentre study.
The diagnosis of sepsis in critically ill patients is challenging because traditional markers of infection are often misleading. The present study was conducted to determine the procalcitonin level at early diagnosis (and differentiation) in patients with systemic inflammatory response syndrome (SIRS) and sepsis, in comparison with C-reactive protein, IL-2, IL-6, IL-8 and tumour necrosis factor-α.
Thirty-three intensive care unit patients were diagnosed with SIRS, sepsis or septic shock, in accordance with the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria. Blood samples were taken at the first and second day of hospitalization, and on the day of discharge or on the day of death. For multiple group comparisons one-way analysis of variance was applied, with post hoc comparison. Sensitivity, specificity and predictive values of PCT and each cytokine studied were calculated.
PCT, IL-2 and IL-8 levels increased in parallel with the severity of the clinical condition of the patient. PCT exhibited a greatest sensitivity (85%) and specificity (91%) in differentiating patients with SIRS from those with sepsis. With respect to positive and negative predictive values, PCT markedly exceeded other variables.
In the present study PCT was found to be a more accurate diagnostic parameter for differentiating SIRS and sepsis, and therefore daily determinations of PCT may be helpful in the follow up of critically ill patients.
C-reactive protein; cytokine; diagnosis; procalcitonin; sepsis
Differentiating between sterile inflammation and bacterial infection in critically ill patients with fever and other signs of the systemic inflammatory response syndrome (SIRS) remains a clinical challenge. The objective of our study was to mine an existing genome-wide expression database for the discovery of candidate diagnostic biomarkers to predict the presence of bacterial infection in critically ill children.
Genome-wide expression data were compared between patients with SIRS having negative bacterial cultures (n = 21) and patients with sepsis having positive bacterial cultures (n = 60). Differentially expressed genes were subjected to a leave-one-out cross-validation (LOOCV) procedure to predict SIRS or sepsis classes. Serum concentrations of interleukin-27 (IL-27) and procalcitonin (PCT) were compared between 101 patients with SIRS and 130 patients with sepsis. All data represent the first 24 hours of meeting criteria for either SIRS or sepsis.
Two hundred twenty one gene probes were differentially regulated between patients with SIRS and patients with sepsis. The LOOCV procedure correctly predicted 86% of the SIRS and sepsis classes, and Epstein-Barr virus-induced gene 3 (EBI3) had the highest predictive strength. Computer-assisted image analyses of gene-expression mosaics were able to predict infection with a specificity of 90% and a positive predictive value of 94%. Because EBI3 is a subunit of the heterodimeric cytokine, IL-27, we tested the ability of serum IL-27 protein concentrations to predict infection. At a cut-point value of ≥5 ng/ml, serum IL-27 protein concentrations predicted infection with a specificity and a positive predictive value of >90%, and the overall performance of IL-27 was generally better than that of PCT. A decision tree combining IL-27 and PCT improved overall predictive capacity compared with that of either biomarker alone.
Genome-wide expression analysis has provided the foundation for the identification of IL-27 as a novel candidate diagnostic biomarker for predicting bacterial infection in critically ill children. Additional studies will be required to test further the diagnostic performance of IL-27.
The microarray data reported in this article have been deposited in the Gene Expression Omnibus under accession number GSE4607.
Blood stream infections (BSI) are life-threatening infections in intensive care units (ICU), and prognosis is highly dependent on early detection. Procalcitonin levels have been shown to accurately and quickly distinguish between BSI and noninfectious inflammatory states in critically ill patients. It is, however, unknown to what extent a recent history of sepsis (namely, secondary sepsis) can affect diagnosis of BSI using PCT.
review of the medical records of every patient with BSI in whom PCT dosage at the onset of sepsis was available between 1st September, 2006 and 31st July, 2007.
179 episodes of either primary (n = 117) or secondary (n = 62) sepsis were included. Procalcitonin levels were found to be markedly lower in patients with secondary sepsis than in those without (6.4 [9.5] vs. 55.6 [99.0] ng/mL, respectively; p < 0.001), whereas the SOFA score was similar in the two groups. Although patients in the former group were more likely to have received steroids and effective antibiotic therapy prior to the BSI episode, and despite a higher proportion of candidemia in this group, a low PCT value was found to be independently associated with secondary sepsis (Odd Ratio = 0.33, 95% Confidence Interval: 0.16–0.70; p = 0.004). Additional patients with suspected but unconfirmed sepsis were used as controls (n = 23). Thus, diagnostic accuracy of PCT as assessed by the area under the receiver-operating characteristic curves (AUROCC) measurement was decreased in the patients with secondary sepsis compared to those without (AUROCC = 0.805, 95% CI: 0.699–0.879, vs. 0.934, 95% CI: 0.881–0.970, respectively; p < 0.050).
In a critically ill patient with BSI, PCT elevation and diagnosis accuracy could be lower if sepsis is secondary than in those with a first episode of infection.
Procalcitonin (PCT) has been widely investigated for its prognostic value in septic patients. However, studies have produced conflicting results. The purpose of the present meta-analysis is to explore the diagnostic accuracy of a single PCT concentration and PCT non-clearance in predicting all-cause sepsis mortality. We searched PubMed, Embase, Web of Knowledge and the Cochrane Library. Articles written in English were included. A 2 × 2 contingency table was constructed based on all-cause mortality and PCT level or PCT non-clearance in septic patients. Two authors independently evaluated study eligibility and extracted data. The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model. We used the Q-test and I2 index to test heterogeneity. Twenty-three studies with 3,994 patients were included. An elevated PCT level was associated with a higher risk of death. The pooled relative risk (RR) was 2.60 (95% confidence interval (CI), 2.05–3.30) using a random-effects model (I2 = 63.5%). The overall area under the summary receiver operator characteristic (SROC) curve was 0.77 (95% CI, 0.73–0.80), with a sensitivity and specificity of 0.76 (95% CI, 0.67–0.82) and 0.64 (95% CI, 0.52–0.74), respectively. There was significant evidence of heterogeneity for the PCT testing time (P = 0.020). Initial PCT values were of limited prognostic value in patients with sepsis. PCT non-clearance was a prognostic factor of death in patients with sepsis. The pooled RR was 3.05 (95% CI, 2.35–3.95) using a fixed-effects model (I2 = 37.9%). The overall area under the SROC curve was 0.79 (95% CI, 0.75–0.83), with a sensitivity and specificity of 0.72 (95% CI, 0.58–0.82) and 0.77 (95% CI, 0.55–0.90), respectively. Elevated PCT concentrations and PCT non-clearance are strongly associated with all-cause mortality in septic patients. Further studies are needed to define the optimal cut-off point and the optimal definition of PCT non-clearance for accurate risk assessment.
Mid-regional pro-adrenomedullin (MR-proADM) has a good biomarker profile: its half-life is several hours, and its plasma concentrations can be determined in clinical practice, it is essentially irrelevant, but proportionally represents the levels and activity of adrenomedullin (ADM). ADM synthesis is widely distributed in tissues, including bone, adrenal cortex, kidney, lung, blood vessels and heart. Its fundamental biological effects include vasodilator, positive inotropic, diuretic, natriuretic and bronchodilator. It has been described high levels in septic patients, interacting directly with the relaxation of vascular tone, triggering hypotension of these patients. It is also found high levels in other diseases such as hypertension, heart failure, respiratory failure, renal failure, cirrhosis and cancer. MR-proADM has been identified as a prognostic marker, stratifying the mortality risk in patients with sepsis in emergency department (ED) and ICU. Evolutionary MR-proADM levels and clearance marker to the 2nd–5th days of admission help to determine the poor performance and the risk of mortality in patients with severe sepsis admitted to the ICU. The MR-proADM levels are more effective than procalcitonin (PCT) and C-reactive protein (CRP) levels to determine an unfavorable outcome and the risk of mortality in patients with sepsis admitted to the ICU. It has also proved useful in patients diagnosed with organ dysfunction of infectious etiology. MR-proADM levels are independent of the germ conversely it is related to the magnitude of organ failure and therefore severity. We consider advisable incorporating the MR-proADM the panel of biomarkers necessary for the diagnosis and treatment of critically ill patients admitted to the ICU with severe sepsis. The combined PCT and MR-proADM levels could represent a valid tool in the clinical practice to timely identify patients with bacterial infections and guide the diagnosis and treatment of sepsis and septic shock.
Mid-regional pro-adrenomedullin (MR-proADM); adrenomedullin (ADM); biomarker; sepsis; septic shock
Systemic inflammatory response syndrome is common after surgery, and it can be difficult to discriminate between infection and inflammation. We performed a review of the literature with the aims of describing the evolution of serum procalcitonin (PCT) levels after uncomplicated cardiac surgery, characterising the role of PCT as a tool in discriminating infection, identifying the relation between PCT, organ failure, and severity of sepsis syndromes, and assessing the possible role of PCT in detection of postoperative complications and mortality.
We performed a search on MEDLINE using the keyword 'procalcitonin' crossed with 'cardiac surgery,' 'heart,' 'postoperative,' and 'transplantation.' Our search was limited to human studies published between January 1990 and June 2006.
Uncomplicated cardiac surgery induces a postoperative increase in serum PCT levels. Peak PCT levels are reached within 24 hours postoperatively and return to normal levels within the first week. This increase seems to be dependent on the surgical procedure and on intraoperative events. Although PCT values reported in infected patients are generally higher than in non-infected patients after cardiac surgery, the cutoff point for discriminating infection ranges from 1 to 5 ng/ml, and the dynamics of PCT levels over time may be more important than absolute values. PCT is superior to C-reactive protein in discriminating infections in this setting. PCT levels are higher with increased severity of sepsis and the presence of organ dysfunction/failure and in patients with a poor outcome or in those who develop postoperative complications. PCT levels typically remain unchanged after acute rejection but increase markedly after bacterial and fungal infections. Systemic infections are associated with greater PCT elevation than is local infection. Viral infections are difficult to identify based on PCT measurements.
The dynamics of PCT levels, rather than absolute values, could be important in identifying patients with infectious complications after cardiac surgery. PCT is useful in differentiating acute graft rejection after heart and/or lung transplantation from bacterial and fungal infections. Further studies are needed to define cutoff points and to incorporate PCT levels in useful prediction models.
Rapid treatment of sepsis is of crucial importance for survival of patients. Specific and rapid markers of bacterial infection have been sought for early diagnosis of sepsis. One such measurement, Procalcitonin (PCT), has recently become of interest as a possible marker of the systemic inflammatory response to infection.
This study was done to find out the common sources of sepsis and to evaluate the diagnostic value of PCT, its predictive value and its relation with Sepsis-related Organ Failure Assessment (SOFA) scores and mortality in various stages of sepsis.
Settings and Design:
The prospective study was conducted at our tertiary care center from October 2006 to December 2008. A total of 100 patients were included in the study. The study sample included all patients aged above 18 years presenting consecutively to our center during the study period with acute sepsis. They were divided into three groups: sepsis, severe sepsis and septic shockbased on standardized criteria.
Materials and Methods:
PCT and various other relevant factors were measured in all study subjects. These parameters were compared among the three study groups. The statistical analyses were done using Student “t” test and two-way analysis of variance (ANOVA).
Respiratory tract infection was the most common source of sepsis. PCT proved to be an excellent indicator of sepsis with sensitivity of 94%. There was a significant association between serum PCT and SOFA scores (P < 0.05). Serum PCT levels did not predict mortality in the present study.
PCT is among the most promising sepsis markers, capable of complementing clinical signs and routine lab parameters suggestive of severe infection.
Procalcitonin; sepsis; septic shock; severe sepsis; sepsis-related organ failure assessment score