Showing papers on "Procalcitonin published in 2006"

Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial.

Abstract: Rationale: In patients with community-acquired pneumonia, guidelines recommend antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial infections, and its dynamics have prognostic implications.Objective: To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia.Methods: In a randomized intervention trial, 302 consecutive patients with suspected community-acquired pneumonia were included. Data were assessed at baseline, after 4, 6, and 8 d, and after 6 wk.The control group (n = 151) received antibiotics according to usual practice. In the procalcitonin group (n = 151), antibiotic treatment was based on serum procalcitonin concentrations as follows: strongly discouraged, less than 0.1 μg/L; discouraged, less than 0.25 μg/L; encouraged, greater than 0.25 μg/L; strongly encouraged, greater than 0.5 μg/L. The primary endpoint was antibiotic use; secondary endpoints were measures of clinical, laboratory, and radiographic outcome.Res...

Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis.

Abstract: Objective:To quantify the accuracy of serum procalcitonin as a diagnostic test for sepsis, severe sepsis, or septic shock in adults in intensive care units or after surgery or trauma, alone and compared with C-reactive protein. To draw and compare the summary receiver operating characteristics curve

Procalcitonin increase in early identification of critically ill patients at high risk of mortality.

Abstract: Objective:To investigate day-by-day changes in procalcitonin and maximum obtained levels as predictors of mortality in critically ill patients.Design:Prospective observational cohort study.Setting:Multidisciplinary intensive care unit at Rigshospitalet, Copenhagen University Hospital, a tertiary ref

Biochemical markers of acute pancreatitis

Abstract: Serum amylase remains the most commonly used biochemical marker for the diagnosis of acute pancreatitis, but its sensitivity can be reduced by late presentation, hypertriglyceridaemia, and chronic alcoholism. Urinary trypsinogen‐2 is convenient, of comparable diagnostic accuracy, and provides greater (99%) negative predictive value. Early prediction of the severity of acute pancreatitis can be made by well validated scoring systems at 48 hours, but the novel serum markers procalcitonin and interleukin 6 allow earlier prediction (12 to 24 hours after admission). Serum alanine transaminase >150 IU/l and jaundice suggest a gallstone aetiology, requiring endoscopic retrograde cholangiopancreatography. For obscure aetiologies, serum calcium and triglycerides should be measured. Genetic polymorphisms may play an important role in “idiopathic” acute recurrent pancreatitis.

Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients

Abstract: Risk stratification of severely ill patients remains problematic, resulting in increased interest in potential circulating markers, such as cytokines, procalcitonin and brain natriuretic peptide. Recent reports have indicated the usefulness of plasma DNA as a prognostic marker in various disease states such as trauma, myocardial infarction and stroke. The present study assesses the significance of raised levels of plasma DNA on admission to the intensive care unit (ICU) in terms of its ability to predict disease severity or prognosis. Fifty-two consecutive patients were studied in a general ICU. Blood samples were taken on admission and were stored for further analysis. Plasma DNA levels were estimated by a PCR method using primers for the human β-haemoglobin gene. Sixteen of the 52 patients investigated died within 3 months of sampling. Nineteen of the 52 patients developed either severe sepsis or septic shock. Plasma DNA was higher in ICU patients than in healthy controls and was also higher in patients who developed sepsis (192 (65–362) ng/ml versus 74 (46–156) ng/ml, P = 0.03) or who subsequently died either in the ICU (321 (185–430) ng/ml versus 71 (46–113) ng/ml, P < 0.001) or in hospital (260 (151–380) ng/ml versus 68 (47–103) ng/ml, P < 0.001). Plasma DNA concentrations were found to be significantly higher in patients who died in the ICU. Multiple logistic regression analysis determined plasma DNA to be an independent predictor of mortality (odds ratio, 1.002 (95% confidence interval, 1.0–1.004), P = 0.05). Plasma DNA had a sensitivity of 92% and a specificity of 80% when a concentration higher than 127 ng/ml was taken as a predictor for death on the ICU. Plasma DNA may be a useful prognostic marker of mortality and sepsis in intensive care patients.

Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia

Abstract: This study sought to assess the prognostic value of the kinetics of procalcitonin (PCT), C-reactive protein (CRP) and clinical scores (clinical pulmonary infection score (CPIS), Sequential Organ Failure Assessment (SOFA)) in the outcome of ventilator-associated pneumonia (VAP) at an early time point, when adequacy of antimicrobial treatment is evaluated This prospective observational cohort study was conducted in a teaching hospital The subjects were 75 patients consecutively admitted to the intensive care unit from October 2003 to August 2005 who developed VAP Patients were followed for 28 days after the diagnosis, when they were considered survivors Patients who died before the 28th day were non-survivors There were no interventions PCT, CRP and SOFA score were determined on day 0 and day 4 Variables included in the univariable logistic regression model for survival were age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, decreasing ΔSOFA, decreasing ΔPCT and decreasing ΔCRP Survival was directly related to decreasing ΔPCT with odds ratio (OR) = 567 (95% confidence interval 178 to 1803), decreasing ΔCRP with OR = 378 (124 to 1150), decreasing ΔSOFA with OR = 308 (102 to 926) and APACHE II score with OR = 092 (086 to 099) In a multivariable logistic regression model for survival, only decreasing ΔPCT with OR = 443 (108 to 1818) and decreasing ΔCRP with OR = 740 (158 to 3473) remained significant Decreasing ΔCPIS was not related to survival (p = 059) There was a trend to correlate adequacy to survival Fifty percent of the 20 patients treated with inadequate antibiotics and 655% of the 55 patients on adequate antibiotics survived (p = 029) Measurement of PCT and CRP at onset and on the fourth day of treatment can predict survival of VAP patients A decrease in either one of these marker values predicts survival

Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: a systematic review of the literature.

Abstract: Introduction 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.

Procalcitonin, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in community-acquired infections and sepsis: a prospective study

Abstract: Clinicians are in need of better diagnostic markers in diagnosing infections and sepsis. We studied the ability of procalcitonin, lipopolysaccharide-binding protein, IL-6 and C-reactive protein to identify patients with infection and sepsis. Plasma and serum samples were obtained on admission from patients with suspected community-acquired infections and sepsis. Procalcitonin was measured with a time-resolved amplified cryptate emission technology assay. Lipopolysaccharide-binding protein and IL-6 were measured with a chemiluminescent immunometric assay. Of 194 included patients, 106 had either infection without systemic inflammatory response syndrome or sepsis. Infected patients had significantly elevated levels of procalcitonin, lipopolysaccharide-binding protein, C-reactive protein and IL-6 compared with noninfected patients (P < 0.001). In a receiver-operating characteristic curve analysis, C-reactive protein and IL-6 performed best in distinguishing between noninfected and infected patients, with an area under the curve larger than 0.82 (P < 0.05). IL-6, lipopolysaccharide-binding protein and C-reactive protein performed best in distinguishing between systemic inflammatory response syndrome and sepsis, with an area under the curve larger than 0.84 (P < 0.01). Procalcitonin performed best in distinguishing between sepsis and severe sepsis, with an area under the curve of 0.74 (P < 0.01). C-reactive protein, IL-6 and lipopolysaccharide-binding protein appear to be superior to procalcitonin as diagnostic markers for infection and sepsis in patients admitted to a Department of Internal Medicine. Procalcitonin appears to be superior as a severity marker.

Differential diagnostic value of procalcitonin in surgical and medical patients with septic shock.

Abstract: Objective:To assess whether different diagnostic and prognostic cutoff values of procalcitonin should be considered in surgical and in medical patients with septic shock.Design:Prospective observational study.Setting:Intensive care unit of the Avicenne teaching hospital, France.Patients:All patients

Procalcitonin kinetics in the prognosis of severe community-acquired pneumonia

Abstract: Objectives Procalcitonin (PCT) kinetics is a good prognosis marker in infectious diseases, but few studies of community-acquired pneumonia (CAP) have been performed in intensive care units (ICU). We analyzed the relationship between PCT kinetics and outcome in ICU patients with severe CAP.

Procalcitonin, C-reactive protein, white blood cells and SOFA score in ICU: diagnosis and monitoring of sepsis.

Abstract: Aim To determine in critically ill patients the value of procalcitonin (PCT), C-reactive protein (CRP), sequential organ failure assessment (SOFA) score and white blood cell count in diagnosis and monitoring of sepsis Methods Patients admitted to a medicosurgical intensive care unit in a prospective, observational study, were observed consecutively According to ACCP/SCCM Consensus Conference definition were defined 4 groups: SEP-SIS/SS (sepsis, severe sepsis, septic shock), SIRS, No-SIRS and TRAUMA Results Two hundred and fifthy five clinical events on a total of 1826 observation days were observed: 111 SEPSIS/SS, 49 TRAUMA, 45 SIRS and 50 No-SIRS ROC values, in the diagnosis of sepsis, were 088 for PCT, 074 for CRP, 08 for Sepsis score, 074 for SOFA, 062 for neuthrophils granulocytes (p<005) The best cutoff values in the diagnosis of sepsis were 047 ng/mL for PCT and 128 mg/L for CRP PCT and SOFA were higher in septic shock than in severe sepsis and sepsis (p<005 in all cases) The maximum CRP level in SEPSIS/SS was reached only after 24-48 h of observation Admission PCT value of TRAUMA patients whom evolving in septic complication was higher than patients with a favourable course: 34 ng/mL (range 263-1271) vs 12 ng/mL (range 05-52) (p<005) TRAUMA patients with septic complications present an early and quick significant increase of PCT (p<005) Conclusions PCT and CRP may be useful together with bacteriological data in sepsis diagnosis; PCT and SOFA closer correlate with the infection severity; PCT is the better parameter to estimate severity, prognosis or further course of the disease

Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram

Abstract: Objective: To determine normal concentrations of procalcitonin in preterm infants shortly after birth and to assess its accuracy in detecting bacterial infection. Methods: Blood samples of 100 preterm infants were prospectively drawn during the first 4 days of life for determination of procalcitonin concentration. Infants were classified into four groups according to their sepsis status. Results: Mean (SD) gestational age and birth weight were 32 (2.9) weeks and 1682 (500) g respectively. A total of 283 procalcitonin concentrations from healthy infants were plotted to construct nomograms of physiologically raised procalcitonin concentration after birth, stratified by two groups to 24–30 and 31–36 weeks gestation. The peak 95th centile procalcitonin concentration was plotted at 28 hours of age; values return to normal after 4 days of life. Only 12 infants were infected, and 13 of their 16 procalcitonin concentrations after birth were higher than the 95th centile, whereas samples taken at birth were lower. In a multivariable analysis, gestational age, premature rupture of membrane, and sepsis status influenced procalcitonin concentration independently, but maternal infection status did not. Conclusions: The suggested neonatal nomograms of preterm infants are different from those of term infants. Procalcitonin concentrations exceeding the 95th centile may be helpful in detecting congenital infection, but not at birth.

Inflammatory mediators for the diagnosis and treatment of sepsis in early infancy

Abstract: Interleukin-6 (IL-6), interleukin-8 (IL-8), and procalcitonin (PCT) are important parameters in the diagnosis of sepsis and for differentiating between viral and bacterial infection in children. We compared the value of IL-6, IL-8, and PCT with C-reactive protein (CRP) in the diagnosis and treatment of late-onset sepsis among infants admitted to the neonatal intensive care unit (group I) and febrile infants admitted to general hospitals from home (group II). Group I was divided into subgroups Ia, positive blood culture (all Gram-positive cocci); Ib, negative blood culture; and Ic, controls. Group II was divided into subgroups IIa, systemic enterovirus infection, and IIb, no enterovirus infection. Enterovirus was identified by real-time (RT) polymerase chain reaction (PCR) and/or by culture in blood and cerebrospinal fluid (CSF). The positive predictive values of IL-6, IL-8, and PCT (78%, 72%, and 83%, respectively) were better than that of CRP (63%) in the diagnosis of neonatal sepsis. After 48 h of antibiotic treatment, IL-6 and IL-8 levels significantly decreased and PCT stabilized in clinically recovered patients, suggesting that these markers may be useful in distinguishing patients in which antibiotic treatment may be discontinued. Among infants of subgroup IIa, 80%-90% had normal values of IL-6, IL-8, and PCT, whereas CRP was increased in 40%. In conclusion, IL-6, IL-8, and PCT are better parameters than CRP in the diagnosis and follow-up of neonatal sepsis due to coagulase-negative staphylococci (CoNS) and in the exclusion of bacterial infection among those with enteroviral infection among febrile infants presenting from home.

Evaluation of serum C-reactive protein, procalcitonin, tumor necrosis factor alpha, and interleukin-10 levels as diagnostic and prognostic parameters in patients with community-acquired sepsis, severe sepsis, and septic shock

Abstract: The diagnostic value of procalcitonin, C-reactive protein, tumor necrosis factor-alpha, and interleukin-10 levels in differentiating sepsis from severe sepsis and the prognostic value of these levels in predicting outcome were evaluated and compared in patients with community-acquired sepsis, severe sepsis, and septic shock in the first 72 h of admission to the hospital. Thirty-nine patients were included in the study. The severe sepsis and septic shock cases were combined in a single "severe sepsis" group, and all comparisons were made between the sepsis (n=21 patients) and the severe sepsis (n=18 patients) groups. Procalcitonin levels in the severe sepsis group were found to be significantly higher at all times of measurements within the first 72 h and were significantly higher at the 72nd hour in patients who died. Procalcitonin levels that remain elevated at the 72nd hour indicated a poor prognosis. C-reactive protein levels were not significantly different between the groups, nor were they indicative of prognosis. No significant differences in the levels of tumor necrosis factor-alpha were found between the sepsis and severe sepsis groups; however, levels were higher at the early stages (at admission and the 24th hour) in patients who died. Interleukin-10 levels were also higher in the severe sepsis group and significantly higher at all times of measurement in patients who died. When the diagnostic and prognostic values at admission were evaluated, procalcitonin and interleukin-10 levels were useful in discriminating between sepsis and severe sepsis, whereas tumor necrosis factor-alpha and interleukin-10 levels were useful in predicting which cases were likely to have a fatal outcome.

Prognostic value of interleukin 6, procalcitonin, and C-reactive protein levels in intensive care unit patients during first increase of fever.

Abstract: To investigate the prognostic value of interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) in critically ill patients during the first increase of fever, serum levels were measured in 38 patients admitted to intensive care unit of the Department of Medicine, Klinikum Grosshadern, University of Munich, immediately after increase of body temperature more than 38.3 degrees C. Ten healthy controls were also included for comparison. The onset of fever was accompanied by elevated circulating levels of all the 3 markers in comparison with healthy controls. However, only IL-6 levels were significantly higher (P < 0.05) in nonsurvivors (n = 21) compared with survivors. Sensitivity, specificity, positive, and negative predictive values calculated from median levels was higher for IL-6 compared with PCT and CRP. Areas under receiver characteristic operating curves revealed the highest area under the curve for IL-6 in contrast to PCT and CRP. These data suggest that IL-6 rather than PCT or CRP may be an early predictor of mortality in patients with onset of fever and identify patients, who need intensive monitoring to initiate appropriate therapy at an early stage.

Diagnostic value of procalcitonin measurement in febrile patients with systemic autoimmune diseases.

Abstract: Objective To determine the usefulness of plasma procalcitonin (PCT) measurement to suspect infectious etiology in febrile patients with systemic autoimmune disease. Methods PCT, C-Reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) were measured in 44 consecutive inpatients with a diagnosis of systemic autoimmune disease and fever >38 masculine C. After careful microbiologic screening no obvious infection was demonstrated in 24 patients (Group A) while an infectious bacterial complication was diagnosed in 20 cases (Group B). Results Median PCT levels were significantly higher in the group B (1.11 vs 0.24 ng/ml; p = 0.0007), whereas the differences for CRP, WBC and ESR did not reach statistical significance. PCT also exhibited a good sensitivity and specificity (75%) in differentiating patients with infection from those with disease flare. With respect to positive and negative predictive values (71.4% and 78.2%), PCT markedly exceeded the other variables. By analyzing PCT values by disease we identified a false positive subgroup of patients suffering from adult onset Still's disease (AOSD), showing markedly elevated PCT levels in absence of infection. By excluding these patients, PCT showed a very good sensitivity and specificity (73.6% and 89.4%) and the area under receiver operating characteristics (ROC) curve rose from 0.801 to 0.904. Conclusion Our data indicate that elevated PCT concentrations offer good sensitivity and specificity for the diagnosis of systemic bacterial infection in febrile patients with systemic autoimmune diseases. However, in fever associated with AOSD PCT may be elevated even in the absence of infectious complication.

Diagnostic value of signs, symptoms and laboratory values in lower respiratory tract infection.

Abstract: Background Lower respiratory tract infections (LRTI) account for the majority of all antibiotics prescribed in the clinical practice, irrespective of the fact that most cases are self-limiting Using the outcome and microbiology findings as gold standard, we determined sensitivity, specificity, positive and negative predictive values of common used signs and symptoms of bacterial LRTI requiring antibiotic therapy Patients 243 consecutive patients with suspected LRTI admitted to a tertiary care hospital Results Bacterial LRTI requiring antibiotic therapy and self-limiting LRTI were diagnosed in 32 and 86 patients, respectively Assessing these two groups, sputum, dyspnea, crackles, fever and leukocytes (WBC) were insensitive and unspecific parameters for the diagnosis of bacterial LRTI requiring antibiotic therapy Cough was sensitive (938%) but unspecific (58%) The sensitivity of infiltrates, C-reactive protein (CRP) >50 mg/L and procalcitonin (PCT) >01 ng/mL was 969%, 938% and 938%, respectively PCT >025 ng/mL showed the highest specificity (977%), followed by WBC >16 x 109/L (942%) and CRP >100 mg/L (919%) The sensitivity of WBC >16 x 109/L was low (375%) Conclusion The overall sensitivity and specificity of signs and symptoms for bacterial LRTI requiring antibiotic therapy was poor Obtaining a chest-X-ray with infiltrates and determining CRP at a cut-off value of 50 mg/L or PCT at a cutoff value of 01 ng/mL was required to ascertain the need for antibiotics in LRTI

Procalcitonin is not sufficiently reliable to be the sole marker of neonatal sepsis of nosocomial origin

Abstract: It has recently been suggested that serum procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to assess the usefulness of PCT as a marker of neonatal sepsis of nosocomial origin. One hundred infants aged between 4 and 28 days of life admitted to the Neonatology Services of 13 acute-care teaching hospitals in Spain over 1-year with clinical suspicion of neonatal sepsis of nosocomial origin were included in the study. Serum PCT concentrations were determined by a specific immunoluminometric assay. The reliability of PCT for the diagnosis of nosocomial neonatal sepsis at the time of suspicion of infection and at 12–24 h and 36–48 h after the onset of symptoms was calculated by receiver-operating characteristics (ROC) curves. The Youden's index (sensitivity + specificity - 1) was used for determination of optimal cutoff values of the diagnostic tests in the different postnatal periods. Sensitivity, specificity, and the likelihood ratio of a positive and negative result with the 95% confidence interval (CI) were calculated. The diagnosis of nosocomial sepsis was confirmed in 61 neonates. Serum PCT concentrations were significantly higher at initial suspicion and at 12–24 h and 36–48 h after the onset of symptoms in neonates with confirmed sepsis than in neonates with clinically suspected but not confirmed sepsis. Optimal PCT thresholds according to ROC curves were 0.59 ng/mL at the time of suspicion of sepsis (sensitivity 81.4%, specificity 80.6%); 1.34 ng/mL within 12–24 h of birth (sensitivity 73.7%, specificity 80.6%), and 0.69 ng/mL within 36–48 h of birth (sensitivity 86.5%, specificity 72.7%). Serum PCT concentrations showed a moderate diagnostic reliability for the detection of nosocomial neonatal sepsis from the time of suspicion of infection. PCT is not sufficiently reliable to be the sole marker of sepsis, but would be useful as part of a full sepsis evaluation.

Serum procalcitonin measurement contribution to the early diagnosis of candidemia in critically ill patients

Abstract: Candidemia is a life-threatening infection in the ICU whose prognosis is highly dependent on the stage at which it is recognized. Procalcitonin (PCT) levels have been shown to accurately distinguish between bacteremia and noninfectious inflammatory states in critically ill patients with clinical signs of sepsis. Little is known about the accuracy of PCT for the diagnosis of candidemia in this setting. A medical intensive care unit in a teaching hospital. Review of the medical records of every non-neutropenic patient with either bacteremia or candidemia and clinical sepsis in whom PCT dosage at the onset of infection was available between May 2004 and December 2005. Fifty episodes of either bacteremia (n = 35) or candidemia (n = 15) were included. PCT levels were found to be markedly higher in patients with bacteremia than in those with candidemia. Moreover, a low PCT value was found to be an independent predictor of candidemia in the study population. According to the calculation of the area under the receiver operating characteristic curve, PCT was found to be accurate in distinguishing between candidemia and bacteremia (0.96 [0.03]). A PCT level of higher than 5.5 ng/ml yields a 100% negative predictive value and a 65.2% positive predictive value for candidemia-related sepsis. A high PCT value in a critically ill non-neutropenic patient with clinical sepsis is unlikely in the setting of candidemia.

Diagnostic accuracy of procalcitonin and interleukin-6 values for predicting bacteremia and clinical sepsis in febrile neutropenic children with cancer.

Abstract: Early diagnosis of sepsis in patients with febrile neutropenia (FN) remains difficult due to nonspecific clinical and laboratory signs of infection. The most widely used inflammatory marker, C-reactive protein (CRP), is relatively slow to develop, and several sequential determinations are necessary for the most accurate diagnosis of infection [1]. Moreover, these values can be influenced by underlying malignant disease and tissue damage. The diagnostic value of two newer markers of severe infection, interleukin-6 (IL-6) and procalcitonin (PCT), have only recently been studied more extensively in adult cancer patients with FN, with controversial results. In children, such studies are still relatively rare. To our knowledge, only two studies have been published previously on IL-6 and PCT in children with FN [2, 3]. In order to further investigate the usefulness of these markers in children, we conducted a prospective study in which we sequentially determined IL-6 and PCT concentrations in children with FN and compared their diagnostic value with that of CRP. In our study, FN was defined according to the standards outlined by the Immunocompromised Host Society [4], except we measured tympanic instead of oral temperature. Episodes of FN were divided into three groups: group 1, bacteremia and clinical sepsis (i.e., septic episode with negative blood cultures); group 2, local infection (i.e., fever with clinically and/or microbiologically proven signs of local infection); and group 3, fever of unknown origin (FUO). From each patient, two consecutive blood samples were obtained from the peripheral vein and central venous catheter for bacterial and fungal cultures, and urine, stool and throat swabs were obtained for bacterial cultures. Complete blood cell counts and CRP measurements were performed daily. In addition, 2 ml of blood was obtained on three consecutive days from each patient for PCT and IL-6 measurement. PCTwas determined using an immunoluminometric assay (LUMItest PCT, BRAHMS Diagnostica, Germany; determination range 0.3–500 μg/l), IL-6 using an immunoenzymatic method (Quantikine, R&D Systems, Germany; determination range 0.7–300 pg/ ml) and CRP using an immunoturbidimetric method (QuickRead CRP, Orion Diagnostica, Finland; determination range 8–160 mg/l). Comparisons were made using Mann-Whitney and Kruskal-Wallis nonparametric tests. Receiver operating characteristic (ROC) curves were used for determining the diagnostic accuracy of PCT, IL-6 and CRP measurements. Areas under the curve (AUC) were compared according to the method described by Hanley and McNeil [5]. A p value of <0.05 was considered significant. Statistical analysis was performed using MedCalc for Windows (version 5.0; MedCalc Software, Mariakerke, Belgium) and SPSS for Windows (version 10.0; SPSS, Chicago, IL, USA). Thirty-two pediatric patients (21 boys, 11 girls) with a median age of 7.6 years (range 1–18 years) who experienced a total of 68 episodes of FN were enrolled in the study. Underlying disease was hematologic malignancy in 50 of 68 episodes and solid tumor in 18 of 68 episodes. The initial neutrophil count was <0.5×10/l in 65 of 68 episodes and 0.5–1×10/l in 3 of 68 episodes in which neutrophil count decreased to <0.5×10/l the next day. L. Kitanovski (*) . J. Jazbec Department of Pediatrics, Division of Oncology and Hematology University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, Slovenia e-mail: lidija.kitanovski@kclj.si Tel.: +386-1-2324298 Fax: +386-1-5229360

Circulating levels of pro‐atrial natriuretic peptide in lower respiratory tract infections

Abstract: . Objective. To analyse the mid region of plasma N-terminal pro-atrial natriuretic peptide (MR-proANP) levels in patients with lower respiratory tract infections to evaluate its prognostic use for the severity of disease and outcome. Design. Prospective observational study. Setting. Emergency department of a university hospital. Subjects. A total of 545 consecutive patients with lower respiratory tract infections and 50 healthy controls. Interventions. MR-proANP was measured in serum from all patients using a new sandwich immunoassay. Results. MR-proANP levels (median [IQR], in pmol L−1) were significantly higher in patients with lower respiratory tract infections when compared with controls (138.0 [74.1–279.0] vs. 72.7 [62.5–89.5], P < 0.001), with highest levels in patients with community-acquired pneumonia (CAP). MR-proANP, but not C-reactive protein (CRP) levels, gradually increased with increasing severity of CAP, classified according to the pneumonia severity index (PSI) score (P < 0.001). On admission, MR-proANP levels were significantly higher in nonsurvivors when compared with survivors (293.0 [154.0–633.0] vs. 129.0 [71.4–255.0], P < 0.001). In a receiver operating characteristic (ROC) analysis for the prediction of survival of patients with CAP the area under the ROC curve (AUC) for MR-proANP was 0.69, similar when compared with the PSI (AUC 0.74, P = 0.31), and better when compared with other biomarkers, i.e. procalcitonin (AUC 0.57, P = 0.08), CRP (AUC 0.52, P = 0.02), and leucocyte count (AUC 0.56, P = 0.07). Conclusions. MR-proANP levels are increased in lower respiratory tract infections, especially in CAP. Together with other clinical, radiographic and laboratory findings, MR-proANP levels might be helpful for the risk stratification in CAP.

Utility of procalcitonin concentration in the evaluation of patients with malignant diseases and elevated c-reactive protein plasma concentrations

Abstract: Background. Elevated plasma concentrations of the C-reactive protein (CRP) are frequently found in patients with malignant diseases. Discrimination between infection and noninfectious acute-phase reactions is essential for therapeutic decisions. Methods. Because increased procalcitonin (PCT) concentrations have been described predominantly in patients with a systemic infection, PCT plasma concentrations were measured prospectively in 111 patients with a hemato-oncological condition with a CRP concentration >8 mg/L. Results. Documented cases of infection were identified in 42 patients, 39 patients had unexplained fever, and 30 patients had no signs of infection. Twenty patients in the latter group were classified as having an elevated CRP concentration caused by a high tumor load (tumor group), and 8 had elevated concentrations that were drug related (drug group). Median CRP concentrations did not differ significantly between groups of patients with and without infection. PCT concentrations were higher in patients with an infection than in patients without an infection and were within the normal range in all patients in the drug and tumor groups. As shown by receiver operating characteristic analysis, PCT concentration was a significant discriminator between having and not having infection, having infection and being in the tumor group, and having infection and being in the drug group. In contrast, CRP concentration was only a predictor of being in the drug group, when the cut-off point was set at 85.1 mg/L, which limited its clinical applicability. Conclusions. PCT concentration contributes significantly to the differential diagnosis for elevated CRP concentrations in patients with hemato-oncological conditions and facilitates therapeutic decisions.

The role of procalcitonin as a predictor of nosocomial sepsis in preterm infants.

Abstract: Aim: To assess the role of procalcitonin in detecting nosocomial sepsis in preterm infants, after the onset of clinical symptoms. Subjects: 100 preterm infants, 24–36 wk of gestation, were followed from the age of 3 d until discharge. Procalcitonin and C-reactive protein (CRP) levels were measured within 3 d of sepsis workup events. Results: 141 blood samples were drawn from 36 infants during 85 episodes of sepsis workup performed between 4 and 66 d of life. Of these episodes, 51 (60%) were not a result of documented sepsis and thereby served as the negative comparison group. Median procalcitonin levels were higher in the septic group compared with the non-septic group at the time of the sepsis workup (2.7 vs 0.5 ng/ml, p=0.003), at 1–24 h after the sepsis workup (4.6 vs 0.6 ng/ml, p=0.003), and at 25–48 h (6.9 vs 2.0 ng/ml, p=0.016). Using high cutoff levels, both procalcitonin (2.3 ng/ml) and CRP (30 mg/l) had high specificity and positive predictive value (97%, 91% and 96%, 87%, respectively) but low sensitivity (48% and 41%, respectively) to detect sepsis. Areas under the ROC curve for procalcitonin and CRP were 0.74 and 0.73, respectively. Conclusion: Procalcitonin >2.3 ng/ml or CRP >30 μg/l indicates a high likelihood for neonatal sepsis, and antibiotic therapy should be continued even in the presence of sterile cultures.

Clinical significance of serum procalcitonin levels in patients with acute or chronic liver disease.

Abstract: Objective To evaluate the diagnostic value of serum procalcitonin levels in patients with acute or chronic liver disease, with or without bacterial infections and to correlate the results with the clinical outcome and the laboratory findings for these patients. Methods One hundred and six consecutive hospitalized patients with liver disease were evaluated for procalcitonin levels on admission. Fifteen of them (14.2%) had acute alcoholic hepatitis on cirrhotic background (group A), 20 (18.9%) had alcoholic cirrhosis without hepatitis and/or bacterial infection (group B), 16 (15.1%) had decompensated cirrhosis with proved bacterial infection (group C), 42 (39.6%) had uncomplicated viral hepatitis-related cirrhosis (group D) and 13 (12.3%) had acute icteric viral hepatitis (group E). Serum procalcitonin levels were measured using an immunoluminometric assay. Statistical analysis was based on Student's t-test and the non-parametric Kruskall-Wallis test (P Results Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (9.80+/-16.80 ng/ml) than in those without bacterial infection (0.21+/-0.13 ng/ml, P=0.001), whereas they were within normal range ( Conclusion Serum procalcitonin levels remain below the threshold of 0.5 ng/ml in all patients with uncomplicated cirrhosis, irrespective of the cause of the disease, while they are significantly elevated when bacterial infection complicates the course of the disease. A significant proportion of patients with acute alcoholic hepatitis on a cirrhotic background as well as of patients with acute on chronic viral hepatitis, without bacterial infection, exhibit serum procalcitonin levels above 0.5 ng/ml, suggesting that this cut-off value is probably not enough to discriminate between patients with or without bacterial infection within these subgroups of patients with liver disease.

Activated partial thromboplastin time waveform analysis: a new tool to detect infection?

Abstract: Objective: An abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time (aPTT) has been described to identify a high-risk intensive care unit population consisting of patients with sepsis or with higher mortality rates than patients with normal aPTT waveforms. We investigated the abnormal aPTT biphasic waveform as a diagnostic and prognostic marker of infection. Design: Prospective, observational study investigating the predictive value of aPTT waveform analysis for the diagnosis and prognosis of sepsis. Setting: Surgical intensive care unit of a university hospital. Patients: We studied 187 consecutive patients who fulfilled at least two or more criteria of the systemic inflammatory response syndrome at admission or during intensive care stay and classified as having systemic inflammatory response syndrome, sepsis, severe sepsis, or septic shock during an 8-month period. Interventions: Laboratory analyses including aPTT waveform analysis and procalcitonin and C-reactive protein concentrations were measured at days 1–3. Measurements and Main Results: The final diagnoses were systemic inflammatory response syndrome in 49%, sepsis in 16%, severe sepsis in 12%, and septic shock in 23% of patients. On day 1, the biphasic waveform was significantly more abnormal in patients with severe sepsis or septic shock than in patients with systemic inflammatory response syndrome or sepsis. The biphasic waveform was more accurate than procalcitonin and C-reactive protein for differentiating patients with severe sepsis and septic shock, with 90% sensitivity and 92% negative predictive value. Biphasic waveform values were significantly more abnormal during days 1–3 in septic nonsurvivors than in survivors and nonseptic nonsurvivors. The biphasic waveform exhibited the best specificity (91%) and negative predictive value (98%) for the prognosis of sepsis-related mortality on day 3. Conclusions: In intensive care units, when the analyzer is available, aPTT waveform analysis is an inexpensive, rapid, effective, and readily available tool providing information for the diagnosis of severe sepsis and the prognosis of septic patients.

Procalcitonin kinetics in pediatric patients with systemic inflammatory response after open heart surgery

Abstract: To evaluate procalcitonin and C-reactive protein as markers of inflammation severity and their value in predicting development of organ failure after pediatric open heart surgery. Prospective, observational, clinical study. Single university hospital. Thirty-three pediatric patients with systemic inflammatory response syndrome (SIRS; n = 19) and SIRS+organ failure (SIRS+OF; n = 14) following open heart surgery were included. Plasma procalcitonin and C-reactive protein levels were measured before and after the operation, and 1, 2, 3, and 4 days after surgery. Patients were evaluated daily to assess organ failure. Postoperative procalcitonin levels in the SIRS+OF group were significantly higher than in the SIRS group. C-reactive protein levels were similar between the groups throughout the study period. Peak procalcitonin levels were found to be positively correlated with aortic cross-clamp and cardiopulmonary bypass times, duration of mechanical ventilation, intensive care unit and hospital stay, mortality and organ failure development. Peak procalcitonin was found to be a good predictor of postoperative organ failure development and mortality. However, the predictive value of peak C-reactive protein for organ failure and mortality was found to be weak. Double-peak procalcitonin curves were observed in SIRS+OF patients with infection during the intensive care unit stay. In the SIRS+OF group peak procalcitonin levels were found to be highly predictive for mortality and organ failure development, whereas C-reactive protein levels were not. Daily procalcitonin measurements in SIRS+OF patients may help identify the postoperative infection during the follow-up period.

Usefulness of C-Reactive Protein to Define Pneumococcal Conjugate Vaccine Efficacy in the Prevention of Pneumonia

Abstract: Objectives and Methods: This study explored whether C-reactive protein (CRP) and/or procalcitonin levels were useful to measure vaccine efficacy (VE) and impact against the burden of pneumonia of a 9-valent pneumococcal conjugate vaccine (PCV), compared with chest radiograph-confirmed alveolar consolidation (CXR-AC) as an outcome Sera obtained from children participating in a phase 3 PCV efficacy trial who were hospitalized for treatment of clinically diagnosed lower respiratory tract infection (C-LRTI) were retrospectively analyzed for CRP and procalcitonin measurements Results: For non-human immunodeficiency virus (HIV)-infected children, the VE estimates for C-LRTI with CRP levels of ≥40 mg/dL (VE 263%; P = 0003) or CRP levels of ≥120 mg/dL (VE 410%; P = 0003) were 17-fold (P = 0002) and 27-fold (P < 00001) greater, respectively, than that for CXR-AC (VE 151%; P = 015) The sensitivity of CXR-AC as an outcome to detect the burden of pneumonia prevented by PCV was 44% (95% confidence interval, 36-55%) in comparison with C-LRTI with CRP levels of ≥40 mg/dL and 73% (95% confidence interval, 58-92%) in comparison with C-LRTI with CRP levels of ≥120 mg/dL CRP also helped to measure the PCV efficacy for children with C-LRTI but the absence of CXR-AC, for whom the outcome of C-LRTI with CRP levels of ≥40 mg/dL (VE 315%; P = 0007) increased the VE estimate 198-fold (P < 00001) in comparison with C-LRTI alone (VE 16%; P = 078) and 32-fold (P = 0005) in comparison with WHO-defined severe pneumonia (VE 100%; P = 017) Although there was a significant correlation between CRP and procalcitonin levels (Spearman's p = 045; P < 00001), the use of procalcitonin levels did not improve either the specificity or sensitivity of measuring the effect of PCV against pneumonia for non-HIV-infected children The observations were similar for HIV-infected children Conclusions: CRP levels of ≥40 mg/dL provide a better measure than chest radiographs to assess the effect of PCV in preventing pneumonia