Showing papers on "Procalcitonin published in 2008"

Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial

Abstract: Rationale: The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance.Objectives: To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock.Methods: In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 μg/L) or Day 5 (if baseline PCT levels were ⩾1 μg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules.Measurements and Main Results: Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control s...

Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations.

Abstract: Objective:The use of procalcitonin (ProCT) as a marker of several clinical conditions, in particular, systemic inflammation, infection, and sepsis, will be clarified, and its current limitations will be delineated. In particular, the need for a more sensitive assay will be emphasized. For these purp

Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care.

Abstract: were restricted was 0.14 with procalcitonin-guided therapy (95% confidence interval [CI], �0.53 to 0.81 days), which met our criterion of an increase in days in which activities were restricted by no more than 1 day. With procalcitonin-guided therapy, the antibiotic prescription rate was 72% lower (95% CI, 66%-78%) than with standard therapy. Both approaches led to a similar proportion of patients reporting symptoms of ongoing or relapsing infection at 28 days (adjusted odds ratio, 1.0 [95% CI, 0.7-1.5]). Conclusions: As an adjunct to guidelines, procalcitoninguidedtherapymarkedlyreducesantibioticuseforacuterespiratory tract infections in primary care without compromising patient outcome. In practice, this could be achieved with1to2procalcitoninmeasurementsinpatientsforwhom the physician intends to prescribe antibiotics. Trial Registration: isrctn.org I dentifier: ISRCTN73182671

Procalcitonin predicts patients at low risk of death from community-acquired pneumonia across all CRB-65 classes

Abstract: The aim of the present study was to investigate the prognostic value, in patients with community-acquired pneumonia (CAP), of procalcitonin (PCT) compared with the established inflammatory markers C-reactive protein (CRP) and leukocyte (WBC) count alone or in combination with the CRB-65 (confusion, respiratory rate >or=30 breaths x min(-1), low blood pressure (systolic value or=65 yrs) score. In total, 1,671 patients with proven CAP were enrolled in the study. PCT, CRP, WBC and CRB-65 score were all determined on admission and patients were followed-up for 28 days for survival. In contrast to CRP and WBC, PCT levels markedly increased with the severity of CAP, as measured by the CRB-65 score. In 70 patients who died during follow-up, PCT levels on admission were significantly higher compared with levels in survivors. In receiver operating characteristic analysis for survival, the area under the curve (95% confidence interval) for PCT and CRB-65 was comparable (0.80 (0.75-0.84) versus 0.79 (0.74-0.84)), but each significantly higher compared with CRP (0.62 (0.54-0.68)) and WBC (0.61 (0.54-0.68)). PCT identified low-risk patients across CRB classes 0-4. In conclusion, procalcitonin levels on admission predict the severity and outcome of community-acquired pneumonia with a similar prognostic accuracy as the CRB-65 score and a higher prognostic accuracy compared with C-reactive protein and leukocyte count. Procalcitonin levels can provide independent identification of patients at low risk of death within CRB-65 (confusion, respiratory rate >or=30 breaths x min(-1), low blood pressure (systolic value or=65 yrs) risk classes.

Serum procalcitonin elevation in critically ill patients at the onset of bacteremia caused by either gram negative or gram positive bacteria

Abstract: In the ICU, bacteremia is a life-threatening infection whose prognosis is highly dependent on early recognition and treatment with appropriate antibiotics. Procalcitonin levels have been shown to distinguish between bacteremia and noninfectious inflammatory states accurately and quickly in critically ill patients. However, we still do not know to what extent the magnitude of PCT elevation at the onset of bacteremia varies according to the Gram stain result. Review of the medical records of every patient treated between May, 2004 and December, 2006 who had bacteremia caused by either Gram positive (GP) or Gram negative (GN) bacteria, and whose PCT dosage at the onset of infection was available. 97 episodes of either GN bacteremia (n = 52) or GP bacteremia (n = 45) were included. Procalcitonin levels were found to be markedly higher in patients with GN bacteremia than in those with GP bacteremia, whereas the SOFA score value in the two groups was similar. Moreover, in the study population, a high PCT value was found to be independently associated with GN bacteremia. A PCT level of 16.0 ng/mL yielded an 83.0% positive predictive value and a 74.0% negative predictive value for GN-related bacteremia in the study cohort (AUROCC = 0.79; 95% CI, 0.71–0.88). In a critically ill patient with clinical sepsis, GN bacteremia could be associated with higher PCT values than those found in GP bacteremia, regardless of the severity of the disease.

The Role of Procalcitonin in Febrile Neutropenic Patients: Review of the Literature

Abstract: Background: Procalcitonin (PCT) has been increasingly used as an inflammatory marker to identify patients with systemic infection. Moreover, PCT guidance allowed significant reduction of antibiotic therapy in patients with respiratory disease. The aim of this qualitative review was, therefore, to evaluate the role of PCT measurements in febrile neutropenic patients in differentiating between various causes of fever and to investigate the value of PCT levels in terms of diagnosing infection or predicting outcome in these patients. Patients and methods: A MEDLINE search was performed using the keyword 'procalcitonin' crossed with 'febrile neutropenia', 'neutropenia', 'fever', 'bone marrow transplantation', and 'stem cell transplantation', and limited to human studies published between January 1990 and October 2006. Bibliographies of identified articles were also searched. Predefined variables were collected from the articles, including year of publication, study design, number of patients included, age group, disease group, markers other than PCT, and study results. Results: From the 30 articles included, PCT seems to be able to discriminate fever due to systemic forms of infection from non-infectious etiologies. Patients with fungal infection may have a delayed increase in PCT levels. PCT has a minimal role, if any, in discriminating Gram-negative from Gram-positive infections. PCT may be useful in outcome prediction in patients with febrile neutropenia but is not superior to interleukin-6 or C-reactive protein concentrations for this purpose. Conclusions: Despite lack of standard definitions, heterogeneity of study populations, and small numbers of patients included in some studies, our review provides important insight into the value of PCT as a diagnostic and prognostic tool in patients with febrile neutropenia.

Markers of treatment failure in hospitalised community acquired pneumonia

Abstract: Background: Lack of response to treatment in community acquired pneumonia (CAP) worsens outcome. We evaluated the systemic cytokine profile (tumour necrosis factor α, interleukin (IL)1, IL6, IL8 and IL10), C reactive protein (CRP) and procalcitonin (PCT) in patients with CAP who had treatment failure. Methods: A prospective study was performed in hospitalised patients with CAP. Cytokines, PCT and CRP measurements were obtained on day 1 and after 72 h of treatment. Treatment failure was the endpoint evaluated, with separation of those with early (⩽72 h) or late failure. Results: 453 patients were included: 84 (18%) had treatment failure, of whom 38 (8%) were early failures. Median levels of IL6, PCT and CRP on days 1 and 3 and median levels of IL8 on day 1 were significantly higher in patients with any treatment failure. Logistic regression analysis demonstrated that values above the cut-off points for IL6 (⩾169 pg/ml), IL8 (⩾14 pg/ml) and CRP (⩾21.9 mg/dl) on day 1 had independent predictive value for any treatment failure after adjustment for initial severity; relative risks (OR) found were 1.9, 2.2 and 2.6, respectively. Increased levels for CRP and PCT on day 1 were also independent predictors for early failure. Increased levels for IL6 and CRP were the best predictors of late failure. Conclusions: Serum levels of CRP, IL6 and PCT on days 1 and 3 were independently associated with a higher risk of any treatment failure. Low levels of PCT and CRP on day 1 had a high negative predictive value for early failure.

Inflammatory markers in SIRS, sepsis and septic shock.

Abstract: Despite great advancement in the understanding of the pathophysiology and in the development of novel therapeutic approaches, mortality of sepsis still remains unacceptably high. Adequate laboratory diagnostics represents a major requirement for the improvement of this situation. For a better understanding of the immunological dysregulation in this disease, several markers are now available for routine diagnostics in the clinical laboratory. They include the cytokines interleukin (IL) -6, IL-8, procalcitonin and the LPS-binding protein (LBP). These novel markers will be compared to the conventional procedure of diagnosing inflammatory and infectious disease, such as measurements of C-reactive protein (CRP) as a major acute phase protein and differential blood counting. Important questions addressed in this review are the usefulness of these markers for early diagnosis, their role as prognostic markers and in the risk assessment of patients. Furthermore, we will discuss whether these parameters are to differentiate between systemic inflammatory response syndrome (SIRS) and sepsis at its different degrees. In the case of an infectious nature of the disease, it is important to differentiate between viral or bacterial origin and to monitor the responsiveness of antibiotic therapies. The literature was analysed with focus on the evidence for diagnostic and analytical performance. For this purpose international definition and staging criteria were used in context of criteria for assay performance including sensitivity, specificity, negative and positive predictive values, ROC analysis and other analytical criteria.

The time course of blood C-reactive protein concentrations in relation to the response to initial antimicrobial therapy in patients with sepsis.

Abstract: C-reactive protein (CRP) may be a useful marker of sepsis but its use in the evaluation of response to therapy remains poorly defined. The aim of this study was to define the time course of CRP levels in septic patients according to their response to initial antimicrobial treatment, and to search for possible correlations between CRP levels and other clinical and biological variables. This prospective, observational, multicenter study included all critically ill patients with sepsis admitted to two medico-surgical departments of intensive care in Brussels, Belgium during a 5-month period. CRP levels and standard clinical and biological variables were measured daily from the day of sepsis diagnosis until death, transfer to the general floor, or the seventh day, which ever came first. Patients were divided into three groups according to their clinical course: group 1 — patients with a favorable response to initial antibiotic therapy; group 2 — patients who required a change in antibiotic therapy; group 3 — patients who needed a procedure to control the infection. CRP concentrations decreased more rapidly and to a greater degree in group 1 than in group 2 patients (p = 0.001). An increase in CRP of at least 2.2 mg/dl in the first 48 h was associated with ineffective initial antibiotic therapy with a sensitivity of 77% and a specificity of 67%. No correlation was found between CRP levels and other clinical and biological variables. Changes in CRP levels over the first 48 h of therapy can help to evaluate the response to initial antimicrobial therapy in septic patients.

Usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia

Abstract: To assess the predictive capacity for the diagnosis of ventilator-associated pneumonia (VAP) of serum procalcitonin levels before and on the day it is suspected. Single-center observational study in the intensive care unit of a teaching hospital. Consecutive patients whose serum procalcitonin levels were available on the day that VAP was clinically suspected (day 1) and at some time within the preceding 5 days (“before”). Serum procalcitonin levels were determined on day 1 and “before”. Among the 73 suspected episodes VAP was confirmed by quantitative bronchoalveolar lavage cultures in 32 and refuted in 41. Respective median “before” procalcitonin levels were 1.89 ng/ml (interquartile range 0.18–6.01) and 2.14 (0.76–5.75) in patients with and without VAP, but their respective median day-1 procalcitonin levels did not differ: 1.07 ng/ml (0.39–6.57) vs. 1.40 (0.67–3.39). On day 1 a 0.5 ng/ml procalcitonin threshold had 72% sensitivity but only 24% specificity for diagnosing VAP. Between “before” and day 1, procalcitonin increased in 41% and 15% of patients with and without VAP, respectively. Thus a procalcitonin rise on day 1, compared to its “before” level, had 41% sensitivity and 85% specificity for diagnosing VAP, with respective positive and negative predictive values of 68% and 65%. Crude values and procalcitonin rise had poor diagnostic value for VAP in this particular setting and thus should not be used to initiate antibiotics when VAP is clinically suspected.

Procalcitonin in young febrile infants for the detection of serious bacterial infections.

Abstract: OBJECTIVES. The objectives of the study were (1) to study the test performance of procalcitonin for identifying serious bacterial infections in febrile infants ≤90 days of age without an identifiable bacterial source and (2) to determine an optimal cutoff value to identify infants at low risk for serious bacterial infections. METHODS. A prospective observational study was performed with febrile infants ≤90 days of age presenting to an urban, pediatric, emergency department. Serum procalcitonin levels were measured by using an automated high-sensitivity assay. An optimal procalcitonin cutoff value was selected to maximize sensitivity and negative predictive value for the detection of serious bacterial infections. Infants were classified as having definite, possible, or no serious bacterial infections. RESULTS. A total of 234 infants (median age: 51 days) were studied. Thirty infants (12.8%) had definite serious bacterial infections (bacteremia: n = 4; bacteremia with urinary tract infections: n = 2; urinary tract infections: n = 24), and 12 infants (5.1%) had possible serious bacterial infections (pneumonia: n = 5; urinary tract infections: n = 7). Mean procalcitonin levels for definite serious bacterial infections (2.21 ± 3.9 ng/mL) and definite plus possible serious bacterial infections (2.48 ± 4.6 ng/mL) were significantly higher than that for no serious bacterial infection (0.38 ± 1.0 ng/mL). The area under the receiver operating characteristic curve was 0.82 for definite serious bacterial infections and 0.76 for definite and possible serious bacterial infections. For identifying definite and possible serious bacterial infections, a cutoff value of 0.12 ng/mL had sensitivity of 95.2%, specificity of 25.5%, negative predictive value of 96.1%, and negative likelihood ratio of 0.19; all cases of bacteremia were identified accurately with this cutoff value. CONCLUSIONS. Procalcitonin has favorable test characteristics for detecting serious bacterial infections in young febrile infants. Procalcitonin measurements performed especially well in detecting the most serious occult infections.

Serum procalcitonin and C-reactive protein concentrations to distinguish mildly infected from non-infected diabetic foot ulcers: a pilot study.

Abstract: Aims/hypothesis Infection of diabetic foot ulcers is common; at early stages it is difficult to differentiate between non-infected ulcers (or those colonised with normal flora) and ulcers infected with virulent bacteria that lead to deterioration. This pilot study aimed to assess the diagnostic accuracy of inflammatory markers as an aid to making this distinction.

Serum procalcitonin level and other biological markers to distinguish between bacterial and aseptic meningitis in children: a European multicenter case cohort study

Abstract: Objective To validate procalcitonin (PCT) level as the best biological marker to distinguish between bacterial and aseptic meningitis in children in the emergency department. Design Secondary analysis of retrospective multicenter hospital-based cohort studies. Setting Six pediatric emergency or intensive care units of tertiary care centers in 5 European countries. Participants Consecutive children aged 29 days to 18 years with acute meningitis. Main Outcome Measures Univariate analysis and meta-analysis to compare the performance of blood parameters (PCT level, C-reactive protein level, white blood cell count, and neutrophil count) and cerebrospinal fluid parameters (protein level, glucose level, white blood cell count, and neutrophil count) quickly available in the emergency department to distinguish early on between bacterial and aseptic meningitis. Results Of 198 patients analyzed, 96 had bacterial meningitis. Sensitivity of cerebrospinal fluid Gram staining was 75%. The PCT level had significantly better results than the other markers for area under the receiver operating characteristic curve (0.98; 95% confidence interval, 0.95-0.99; P = .001). At a 0.5-ng/mL threshold, PCT level had 99% sensitivity (95% confidence interval, 97%-100%) and 83% specificity (95% confidence interval, 76%-90%) for distinguishing between bacterial and aseptic meningitis. The diagnostic odds ratio between high PCT level and bacterial meningitis was 139 (95% confidence interval, 39-498), without significant heterogeneity between centers. Conclusions The PCT level is a strong predictor for distinguishing between bacterial and aseptic meningitis in children in the emergency department. Its combination with other parameters in an effective clinical decision rule could be helpful.

Sequential measurements of procalcitonin levels in diagnosing ventilator-associated pneumonia

Abstract: The utility of procalcitonin levels to improve the accuracy of clinical and microbiological parameters in diagnosing ventilator-associated pneumonia (VAP) was evaluated. Sequential measurement of procalcitonin and C-reactive protein levels and the calculation of the simplified Clinical Pulmonary Infection Scores (CPIS) were performed in 44 patients mechanically-ventilated for >48 h with neither active infection for the duration or suspicion of VAP. Patients who developed extrapulmonary infection were excluded. In total, 20 cases were suspected of having VAP and diagnosis was microbiologically confirmed in nine. In patients with confirmed VAP, procalcitonin levels were higher than in those without VAP. C-reactive protein levels and CPIS were lower in patients without suspected VAP, but could not discriminate confirmed and nonconfirmed suspicion of VAP. The best sensitivity and specificity (78 and 97%, respectively) corresponded to procalcitonin. The CPIS resulted in the same sensitivity, but had a lower specificity (80%). C-reactive protein had the worst sensitivity (56%), but a good specificity (91%). A CPIS >or=6 combined with serum levels of procalcitonin >or=2.99 ng.mL(-1) did not improve the sensitivity (67%), but resulted in 100% specificity. Procalcitonin might be useful in the diagnosis of ventilator-associated pneumonia. Combined values of Clinical Pulmonary Infection Scores and procalcitonin below the cut-off points excluded false-positive diagnoses of ventilator-associated pneumonia.

Evaluation of procalcitonin, neopterin, C-reactive protein, IL-6 and IL-8 as a diagnostic marker of infection in patients with febrile neutropenia.

Abstract: Infectious complications in neutropenic patients are a major cause of morbidity and mortality. Clinical signs are unspecific and fever can be attributed to other causes. Inflammatory biomarkers have emerged as potentially useful in diagnosis of bacterial and fungal infection. Levels of several biomarkers were measured in patients with hematological malignancy at diagnosis and at the beginning of neutropenia due to cytostatic treatment or after hematopoietic stem cell transplantation, and daily until 6 days after presenting fever. Procalcitonin (PCT) and neopterin levels were not elevated at diagnosis or at the beginning of neutropenia. C-reactive protein (CRP) was moderately elevated. PCT levels were significantly higher in patients with Gram-negative bacteremia at 24-48 h after the onset of fever. Patients with probable fungal infection presented elevated PCT values when fever persisted for more than 4-5 days. CRP was more sensitive to predict bacteremia (both Gram-positive and Gram-negative) but the specificity was low. Neither neopterin, IL-6 nor IL-8 presented significant differences according to the origin or etiology of fever. Since it showed a high negative predictive value of Gram-negative bacteremia, clinical prediction rules that attempt to predict a high risk of severe infection might be improved by including measurement of PCT.

The value of clinical features in differentiating between viral, pneumococcal and atypical bacterial pneumonia in children

Abstract: Objective To evaluate the value of clinical features in differentiating between viral, pneumococcal and atypical bacterial pneumonia in children. Design A retrospective analysis of clinical signs and symptoms, supplemented with chest radiograph and serum procalcitonin data, in 101 children with community-acquired pneumonia. Viral and bacterial aetiology was studied prospectively by antibody assays, and pneumococcal infection was found in 18, atypical bacterial infection in 28 and viral infection alone in 22 cases. Methods Chest radiographs and serum procalcitonin were studied in all cases. Data on clinical signs and symptoms were retrospectively collected from the medical cards of the patients. Results Among symptoms, cough was present in 89% and fever (>37.5 degrees C) in 88% of the cases. Among physical signs, crackles were present in 49% and decreased breath sounds in 58%. No significant associations were found between any of the clinical signs or symptoms and the aetiology of pneumonia. In multivariate analyses, age over 5 years and serum procalcitonin over 1.0 ng/mL were the only independent predictors of bacterial aetiology, but no finding was able to screen between pneumococcal and atypical bacterial aetiology of infection. Conclusion No clinical or radiological characteristic was helpful in the separation between viral, pneumococcal and atypical bacterial aetiology of community-acquired pneumonia (CAP) in children.

Prognostic value of mortality in emergency department sepsis score, procalcitonin, and C-reactive protein in patients with sepsis at the emergency department.

Abstract: The prognostic value of procalcitonin (PCT) in patients with sepsis at the emergency department (ED) has not been evaluated. We conducted a prospective observational study to compare the prognostic value of PCT on sepsis and compared with a validated score, Mortality in Emergency Department Sepsis (MEDS) score, and C-reactive protein (CRP) in the setting of ED of an urban, university-based medical center. Five hundred twenty-five consecutive adult patients admitted to the ED fulfilling the American College of Clinical Pharmacists/Society of Critical Care Medicine Consensus Conference definition of sepsis were prospectively enrolled. Serum PCT and CRP were evaluated for each patient. Clinical characteristics and laboratory results on ED admission were recorded using a standardized form. Each patient was followed for at least 30 days. The main outcome was early (5-day) and late (6- to 30-day) mortality. The median age of the study sample was 64.0 (interquartile range, 47-76) years old, and the overall 30-day mortality rate was 10.5%. The c-statistic in the prediction of early mortality was 0.89 for MEDS, 0.76 for PCT, and 0.68 for CRP. The c-statistic in the prediction of late mortality was 0.78 for MEDS, 0.70 for PCT, and 0.63 for CRP. Overall, MEDS score has the best discriminative capability among the three tested markers. Under the best cutoff value, PCT was the most sensitive, and MEDS score was the most specific marker. We suggest further combining the information on PCT and MEDS score to enhance the accuracy in predicting ED sepsis mortality.

The influence of corticosteroids on the release of novel biomarkers in human endotoxemia.

Abstract: Sepsis intervention studies need better patient stratification methods, and one way to realize this is the introduction of stable biomarkers. A set of recently developed novel biomarkers, based upon precursor-fragments of short-lived hormones, was previously shown to be increased during sepsis. However, it is not known whether these biomarkers are influenced by sepsis intervention strategies. Therefore we investigated the markers in a model of human endotoxemia intervened by increasing doses of prednisolone. Prospective, open-label study in a specialized clinical research unit of a university hospital. Thirty-two healthy male volunteers. Subjects received prednisolone orally at doses of 0, 3, 10 or 30 mg (n = 8 per group) at 2 h before intravenous injection of Escherichia coli lipopolysaccharide (LPS) (4 ng/kg). Blood samples were drawn during 24 h after LPS injection. LPS injection caused an increase in levels of midregional pro-adrenomedullin (MR-proADM), midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-arginine–vasopressin (CT-proAVP) and procalcitonin (PCT). Prednisolone caused a dose dependent inhibition of MR-proADM, MR-proANP and CT-proAVP levels. These results show that a set of novel, highly stable sepsis biomarkers was increased during human endotoxemia and was dose-dependently inhibited by corticosteroid pre-treatment.

Procalcitonin and C-reactive protein as markers of bacterial infection in critically ill children at onset of systemic inflammatory response syndrome.

Abstract: OBJECTIVE To compare the accuracy of procalcitonin and C-reactive protein as diagnostic markers of bacterial infection in critically ill children at the onset of systemic inflammatory response syndrome (SIRS). DESIGN Prospective cohort study. SETTING Tertiary care, university-affiliated pediatric intensive care unit (PICU). PATIENTS Consecutive patients with SIRS. INTERVENTIONS From June to December 2002, all PICU patients were screened daily to include cases of SIRS. At inclusion (onset of SIRS), procalcitonin and C-reactive protein levels as well as an array of cultures were obtained. Diagnosis of bacterial infection was made a posteriori by an adjudicating process (consensus of experts unaware of the results of procalcitonin and C-reactive protein). Baseline and daily data on severity of illness, organ dysfunction, and outcome were collected. MEASUREMENTS AND MAIN RESULTS Sixty-four patients were included in the study and were a posteriori divided into the following groups: bacterial SIRS (n = 25) and nonbacterial SIRS (n = 39). Procalcitonin levels were significantly higher in patients with bacterial infection compared with patients without bacterial infection (p = .01). The area under the receiver operating characteristic curve for procalcitonin was greater than that for C-reactive protein (0.71 vs. 0.65, respectively). A positive procalcitonin level (>or=2.5 ng/mL), when added to bedside clinical judgment, increased the likelihood of bacterial infection from 39% to 92%, while a negative C-reactive protein level (<40 mg/L) decreased the probability of bacterial infection from 39% to 2%. CONCLUSIONS Procalcitonin is better than C-reactive protein for differentiating bacterial from nonbacterial SIRS in critically ill children, although the accuracy of both tests is moderate. Diagnostic accuracy could be enhanced by combining these tests with bedside clinical judgment.

Serum procalcitonin for discrimination between septic and non-septic arthritis

Abstract: Background. Early differentiation be- tween septic and non-septic arthritis is diffi cult. A previous study showed promising diagnostic accuracy of se- rum Procalcitonin (PCT) in septic ar- thritis, limited by a low sensitive PCT test kit. Objective. To investigate the diagnos- tic value of PCT in patients with septic and non-septic arthritis using a novel test with low detection limit. Methods. Forty-two patients, 28 with non-septic and 14 with septic arthritis were prospectively included. For each patient, gram stain, culture and po- larization microscopy of synovial fl uid was done and PCT, C-reactive protein (CRP), white blood cell count, uric acid and blood cultures were taken. Patients with septic arthritis, patients with non- septic arthritis with and without con- comitant infection were compared. Results. Patients with septic arthritis had a signifi cant higher PCT concen- tration than patients with non-septic arthritis (p<0.0001). At a cut-off of 0.1 (0.25) ng/ml, sensitivity for septic arthritis was 100(93)% and specifi city 46(75)%. Specifi city rose to 93% after exclusion of patients with non-septic arthritis and concomitant infection. Both sensitivity and specifi city for the diagnosis of septic arthritis were high- er for PCT than CRP. Conclusions. Our data suggest that PCT seems to be a highly sensitive and specifi c marker for septic arthritis, de- pending on the clinical setting. Further studies are warranted.

A score identifying serious bacterial infections in children with fever without source.

Abstract: The objective of the study was to develop a simple clinical tool to identify serious bacterial infection (SBI) in children with fever without a source. For each child, a clinical assessment, a white blood cell count, a urine analysis, a determination of C-reactive protein, procalcitonin, and appropriate cultures were performed. Two hundred two children were studied of whom 54 (27%) had SBI. In the multivariate analysis, only procalcitonin [odds ratio (OR): 37.6], C-reactive protein (OR: 7.8), and urine dipstick (OR: 23.2) remained significantly associated with SBI. The sensitivity of the score for the identification of SBI was 94% and the specificity 81%. In the validation set the sensitivity of the score was 94% and the specificity 78%.

Influence of renal dysfunction on the accuracy of procalcitonin for the diagnosis of postoperative infection after vascular surgery.

Abstract: Objective:Procalcitonin has been advocated as a specific biomarker for bacterial infection. We performed this study to determine whether accuracy of procalcitonin for diagnosis of postoperative bacterial infection is affected by renal function after aortic surgery.Design:Single-center prospective st

Lactate, procalcitonin, and amino-terminal pro-B-type natriuretic peptide versus cytokine measurements and clinical severity scores for prognostication in septic shock.

Abstract: The biomarkers lactate, procalcitonin, and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are often promoted as being useful for prognostication in septic shock. This study aimed to compare the prognostic utility of these biomarkers with each other and with cytokine measurements and clinical severity scores, and to assess how these biomarkers may be combined to improve their prognostic utility. Seventy-two patients with septic shock were studied. The biomarkers were measured on the first 3 days of stay in the intensive care unit together with serum IL-1beta, IL-6, IL-10, and TNF-alpha levels. Although elevated baseline lactate levels predicted 28-day mortality, elevated procalcitonin and NT-proBNP levels were only predictive from days 2 and 3, respectively. The prognostic utility of baseline lactate levels was poorer than that of baseline cytokine levels, the Acute Physiology and Chronic Health Evaluation II score, and the Sequential Organ Failure Assessment score. However, a rising trend in lactate and procalcitonin levels between days 1 and 2 had superior prognostic utility compared with absolute levels. Indeed, using multivariate analysis, the presence of a concurrent increase in both lactate and procalcitonin levels between days 1 and 2 superseded all cytokine measurements and clinical severity scores as the sole independent predictor of 28-day mortality. In conclusion, elevated baseline lactate levels offer superior prognostic accuracy to baseline procalcitonin levels, which in turn are superior to NT-proBNP levels. To improve their prognostic utility beyond those of cytokine measurements and clinical severity scores, serial lactate and procalcitonin measurements may be combined.

Lipopolysaccharide binding protein in a surgical intensive care unit: a marker of sepsis?

Abstract: Objectives: We investigated the time course of lipopolysaccharide binding protein (LBP) plasma concentrations in patients in the surgical intensive care unit (ICU), their value in discriminating sepsis from systemic inflammatory response syndrome, and their association with severity of sepsis and outcome in these patients compared with interleukin (IL)-6, C-reactive protein, and procalcitonin. Design: Prospective, observational, cohort study. Setting: Academic ICU. Patients: All 327 consecutively admitted patients. Measurements and Main Results: Serum LBP concentrations were higher in patients who had severe sepsis/septic shock on ICU admission than in patients who never had sepsis (20.5 [8.1–38.8] vs. 14.2 [7.7–22.2] μg/mL, p .2). LBP concentrations on admission were similar in nonsurvivors and survivors and did not discriminate ICU mortality. However, the maximum LBP concentration during the first 3 days in the ICU discriminated moderately between survivors and nonsurvivors. Conclusions: In the surgical ICU, LBP moderately discriminated patients without infection from patients with severe sepsis but not from patients with sepsis without organ dysfunction. LBP concentrations did not distinguish between Gram-positive and Gram-negative infections. The correlation of LBP concentrations with disease severity and outcome is weak compared with other markers and its use as a biomarker is not warranted in this patient population.

Efficacy of procalcitonin in the early diagnosis of bacterial infections in a critical care unit.

Abstract: Procalcitonin (PCT) is a marker of severe bacterial infections and organ failure due to sepsis. The purpose of the present study was to identify the appropriate cutoff level of PCT based on the findings of a blood culture and polymerase chain reaction (PCR). The PCT levels were measured in 116 patients in an intensive care unit who were suspected of having bacteremia, to examine its relationship with a blood culture or PCR. The PCT levels were significantly high in patients with bacteremia, but they were also moderately high in some patients who were positive for fungus DNA. The area under the curve was significantly higher for PCT than for C-reactive protein. The appropriate cutoff values of PCT for bacteremia were 0.38 μg/L for the high negative predictive value and 0.83 μg/L for the high positive predictive value. Procalcitonin was slightly related to mortality, and the combination of a blood culture and PCR was thus found to increase the sensitivity for mortality. These findings suggest that PCT is useful for the diagnosis of bacteremia and that the diagnostic value of PCT in combination a with blood culture and PCR for bacterial infection or mortality further increases.

Biological markers to determine eligibility in trials for community-acquired pneumonia: a focus on procalcitonin.

Abstract: Clinical features such as cough, sputum production, fever, and the presence of a new lung infiltrate seen on radiograph are not specific to respiratory tract infection, nor do they define the need for antibiotic therapy. Therefore, investigators have looked for biological markers that can supplement clinical information to determine whether the etiology of the infection is more likely bacterial, needing antibiotic therapy, or viral. There are studies of a number of biological markers in serum and bronchoalveolar lavage fluid, including cytokines, acute-phase reactants, and immunoglobulins. The 2 most promising markers in serum are C-reactive protein and procalcitonin (PCT). PCT is a hormokine, produced primarily by parenchymal cells in response to microbial toxins and in response to certain host inflammatory mediators (interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6). Because PCT is down-regulated in the presence of viral infection, PCT seems most promising for defining the need for antibiotic therapy among patients with radiographic evidence of pneumonia. Studies using the highly sensitive Kryptor assay have shown that PCT guidance can lead to the safe withholding of antibiotics among patients with low PCT levels (<0.25 microg/L) and no clinical signs of severe illness. In addition, serial measurements of PCT have been reported to correlate with clinical response to therapy and may be able to guide short durations of therapy. In the future design of trials for community-acquired pneumonia, we may want to exclude patients with low PCT levels, because they are unlikely to benefit from antibiotic therapy. On the other hand, inclusion of patients with low PCT values creates heterogeneity in the study population and confounds the interpretation of clinical trial end points.

Early and late markers for the detection of early-onset neonatal sepsis.

Abstract: Introduction: In this study we tested how a combination of early and late paraclinic markers could predict early onset neonatal sepsis (EONS). Methodology: The first 24 hours after the suspicion of EONS, we measured interleukine (IL)-6, IL-8, IL-10, IL-18, tumor necrosis factor-alpha (TNF-α ), interferon gamma (INF-γ), procalcitonin (PCT) and C-reactive protein (CRP) at 8-hour intervals on 123 neonates clinically suspected for EONS. The neonates were divided into two groups. The sepsis group: 1A with blood culture verified bacteraemia and 1B strongly suspected sepsis (29 patients). The no sepsis group: 2A treated with antibiotics (37 patients) and 2B not treated with antibiotics (57 patients). Results: Combined evaluation of each of the early markers with PCT >25 ng/ml for prediction of EONS at time 0, gave the following sensitivities and specificities: IL-6 >250 pg/ml: 71% and 88%; IL-8 >900 pg/ml: 50% and 88%; IL-10 >40 pg/ml: 43% and 87%; and immature/total (I/T) ratio >0.35: 59% and 88%. The results of IL-18, TNF-α and IFN-γ did not predict EONS. Conclusion: IL-6 combined with PCT values is a fair way to evaluate EONS at the time of suspicion of infection. The “old” early marker, I/T ratio, is almost as efficient as IL-6. By combining an early and a late marker it may be possible to reduce the diagnostic “non-conclusive” period of paraclinic values.