calca-protein--human and Fever-of-Unknown-Origin

The aim of this study was to determine the accuracy of the procalcitonin (PCT) test for diagnosis of bacterial sepsis in pediatric cancer patients with febrile neutropenia.. Three major databases, MEDLINE, EMBASE and the Cochrane Library were searched for studies that evaluated the diagnostic value of PCT alone or compared with other laboratory markers such as C-reactive protein (CRP) to identify bacterial sepsis in children with fever and neutropenia. A bivariate model was used to derive summary sensitivity and specificity of the diagnostic tests.. A total of 10 studies looking into PCT tests and 8 studies looking into CRP tests were included in the final analysis. The prevalence of bacterial sepsis was 304 of 1031 (29.5%) in PCT studies and 741 of 1316 (56.3%) in CRP studies. In terms of area under the receiver operating characteristic curve, PCT had comparable discrimination to CRP (area under the curve: 0.75 versus 0.74). PCT was not as sensitive as the CRP test. The pooled sensitivity of PCT was 0.59 (95% confidence interval [CI]: 0.42-0.74) as compared with 0.75 (95% CI: 0.61-0.85) for CRP. PCT was more specific than sensitive whereas CRP was more sensitive than specific in this population. The pooled specificity was 0.76 (95% CI: 0.64-0.85) for PCT and 0.62 (95% CI: 0.49-0.73) for CRP. PCT had greater likelihood ratio positive (2.50; 95% CI: 1.64-3.81), making it the better rule-in test.. Of three markers potentially useful for diagnosing bacterial sepsis in children with fever and neutropenia, PCT had comparable diagnostic accuracy to CRP.

Topics: Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Fever of Unknown Origin; Humans; Neutropenia; Protein Precursors; Sepsis; Statistics as Topic

We determine the usefulness of the procalcitonin for early identification of young children at risk for severe bacterial infection among those presenting with fever without source.. The design was a systematic review and meta-analysis of diagnostic studies. Data sources were searches of MEDLINE and EMBASE in April 2011. Included were diagnostic studies that evaluated the diagnostic value of procalcitonin alone or compared with other laboratory markers, such as C-reactive protein or leukocyte count, to detect severe bacterial infection in children with fever without source who were aged between 7 days and 36 months.. Eight studies were included (1,883 patients) for procalcitonin analysis, 6 (1,265 patients) for C-reactive protein analysis, and 7 (1,649 patients) for leukocyte analysis. The markers differed in their ability to predict serious bacterial infection: procalcitonin (odds ratio [OR] 10.6; 95% confidence interval [CI] 6.9 to 16.0), C-reactive protein (OR 9.83; 95% CI 7.05 to 13.7), and leukocytosis (OR 4.26; 95% CI 3.22 to 5.63). The random-effect model was used for procalcitonin analysis because heterogeneity across studies existed. Overall sensitivity was 0.83 (95% CI 0.70 to 0.91) for procalcitonin, 0.74 (95% CI 0.65 to 0.82) for C-reactive protein, and 0.58 (95% CI 0.49 to 0.67) for leukocyte count. Overall specificity was 0.69 (95% CI 0.59 to 0.85) for procalcitonin, 0.76 (95% CI 0.70 to 0.81) for C-reactive protein, and 0.73 (95% CI 0.67 to 0.77) for leukocyte count.. Procalcitonin performs better than leukocyte count and C-reactive protein for detecting serious bacterial infection among children with fever without source. Considering the poor pooled positive likelihood ratio and acceptable pooled negative likelihood ratio, procalcitonin is better for ruling out serious bacterial infection than for ruling it in. Existing studies do not define how best to combine procalcitonin with other clinical information.

Topics: Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Fever of Unknown Origin; Humans; Infant; Infant, Newborn; Leukocytosis; Protein Precursors; Risk Factors

To evaluate the diagnostic accuracy of serum procalcitonin (PCT) to detect severe bacterial infection (SBI) in ambulatory children attended in the emergency room (ER) for fever without source (FWS).. A search was made in MEDLINE, OVID and EMBASE (to January 2010). We searched for papers that evaluated the diagnostic accuracy of serum PCT to detect SBI in children that, being previously well, were seen in the ER for FWS. We rated the methodological quality of each paper using objective validity criteria (QUADAS, CASPE) and included only those with the maximum quality in the analysis. The statistical meta-analysis was performed using the software, Meta-DiSc 1.1.1 for Windows.. The search identified 115 papers. Only 6 studies (prospective observational and analytic cohorts) fitted the inclusion criteria, with a sample size of 1139 patients. The prevalence of SBI was between 12.8% and 29% with a weighted mean of 18%. The overall senstivity was 0.771 (95% CI=0.707-0.826), the overall specificity was 0.804 (95% CI=0.777-0.830), the overall positive likelihood ratio was 3.610 (95% CI=2.481-5.253) and the overall negative likelihood ratio was 0.218 (95% CI=0.106-0.446). The diagnostic OR was 18.922 (95% CI=10.076-35.534), the Area under the SROC curve was 0.8801 (95% CI=0.821-0.939), and the optimal diagnostic cut-off value was Q*=0.8106 (95% CI=0.7512-0.8699).. On the basis of our analysis, in children with FWS seen in the ER, the serum PCT test accurately identifies those that have a SBI. We cannot extrapolate these results to other types of patients.

Topics: Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Child; Fever of Unknown Origin; Humans; Protein Precursors; Reproducibility of Results

For decades, many investigators have attempted to identify clinical or laboratory markers that can accurately differentiate severe bacterial from self-limiting viral infections in young children with fever without source. Unfortunately, no perfect marker has been discovered so far. Many guidelines recommend white blood cell count as a screening marker in fever without source, whereas compelling evidence in the literature emphasizes the superior characteristics of C-reactive protein and procalcitonin. One way to improve predictive value is the combination of prediction rules of different tests for clinical and laboratory markers. Several clinical decision rules, reviewed in this article, have been suggested but seem to be difficult to implement in practice due to their complexity. Recently, procalcitonin, C-reactive protein and urinary dipstick were combined in a simple risk index score that displayed promising predictive value in severe bacterial infections in children. Ultimately, impact analyses still have to be performed to show improved quality of care in this setting.

Topics: Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Clinical Trials as Topic; Diagnosis, Differential; Fever of Unknown Origin; Humans; Infant; Infant, Newborn; Leukocyte Count; Protein Precursors; Sensitivity and Specificity; Sepsis; Virus Diseases

The study was performed to assess the usefulness of two new biomarkers, midregional pro-adrenomedullin (MR-pro-ADM) and C-pro-endothelin-1 (CT-pro-ET-1), in predicting bacterial infection (BI) and especially invasive bacterial infection (IBI) in well-appearing infants with fever without source (FWS). For this purpose, a multicenter prospective study was conducted between February 2008 and March 2009 including well-appearing infants less than 36 months of age with FWS. MR-pro-ADM, CT-pro-ET-1, procalcitonin (PCT), CRP, and WBC were measured and compared. Among the 1,035 infants included, a bacterial infection was diagnosed in 75 patients (7.2 %), and 16 (1.54 %) had an invasive bacterial infection (bacterial meningitis, 8; occult bacteremia, 6; and sepsis, 1). MR-pro-ADM and CT-pro-ET-1 levels were less reliable for diagnosis than the other biomarkers. The area under receiver operating characteristic curve for infants with BI and IBI was 0.59 (95 % confidence interval (CI) 0.52-0.67) and 0.63 (95 % CI 0.46-0.80) for MR-pro-ADM and 0.58 (95 % CI 0.51-0.66) and 0.62 (95 % CI 0.47-0.67) for CT-pro-ET-1, respectively. Multivariate analysis showed that PCT ≥ 0.5 ng/mL, CRP ≥ 40 mg/L, and CT-pro-ET-1 ≥ 105 pmol/mL were independent risk factors for having a BI (odds ratio (OR) 6.12, 3.61, and 2.84, respectively). PCT was the only independent risk factor for having an IBI (OR 17.53 if PCT ≥ 0.5 ng/mL).. Although baseline MR-pro-ADM and CT-pro-ET-1 levels are significantly elevated in well-appearing febrile infants with a bacterial infection, their overall performance as diagnostic markers is very poor.

Topics: Adrenomedullin; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Endothelin-1; Female; Fever of Unknown Origin; Follow-Up Studies; Humans; Infant; Leukocyte Count; Logistic Models; Male; Multivariate Analysis; Odds Ratio; Peptide Fragments; Prospective Studies; Protein Precursors; ROC Curve; Severity of Illness Index

To compare the diagnostic properties of procalcitonin (PCT), C reactive protein (CRP), total white blood cells count (WBC), absolute neutrophil count (ANC) and clinical evaluation to detect serious bacterial infection (SBI) in children with fever without source.. Prospective cohort study.. Paediatric emergency department of a tertiary care hospital.. Children aged 1-36 months with fever and no identified source of infection.. Complete blood count, blood culture, urine analysis and culture. PCT and CRP were also measured and SBI probability evaluated clinically with a visual analogue scale before disclosing tests results. Outcome measure Area under the curves (AUC) of the receiver operating characteristic curves.. Among the 328 children included in the study, 54 (16%) were diagnosed with an SBI: 48 urinary tract infections, 4 pneumonias, 1 meningitis and 1 bacteraemia. The AUC were similar for PCT (0.82; 95% CI 0.77 to 0.86), CRP (0.88; 95% CI 0.84 to 0.91), WBC (0.81; 95% CI 0.76 to 0.85) and ANC (0.80; 95% CI 0.75 to 0.84). The only statistically significant difference was between CRP and ANC (Δ AUC 0.08; 95% CI 0.01 to 0.16). It is important to note that all the surrogate markers were statistically superior to the clinical evaluation that had an AUC of only 0.59 (95% CI 0.54 to 0.65).. The study data demonstrate that CRP, PCT, WBC and ANC had almost similar diagnostic properties and were superior to clinical evaluation in predicting SBI in children aged 1 month to 3 years.

Topics: Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Emergency Service, Hospital; Female; Fever of Unknown Origin; Humans; Infant; Leukocyte Count; Male; Neutrophils; Pneumococcal Vaccines; Protein Precursors; Urinary Tract Infections

Clinicians have used procalcitonin (PCT) (biomarker to differentiate bacterial from non-bacterial sepsis) to guide use of antibiotics in patients. As the data for utility of PCT to discontinue antibiotics in an antimicrobial stewardship program (ASP) are lacking, we aim to describe the outcomes of patients in whom PCT was used to discontinue antibiotics under our ASP. An antimicrobial stewardship (AS) team intervened to discontinue antibiotics in patients with persistent fever or leucocytosis, source of sepsis unknown or negative bacteriological cultures, who had completed an adequate course of antibiotic therapy and had a PCT of <0.5 μg/L. Main outcomes evaluated were 14-day re-infection, 30-day mortality and readmission. Antibiotic therapy was discontinued in 42 patients in 1 year. Unknown source of sepsis was found in 38% of the patients (including possible malignant fever) and culture-negative pneumonia was found in 21%. Two patients died of advanced cancer. One patient decided for comfort care and died one week later. One patient died due to a second episode of pneumonia 37 days after first PCT test. Six patients were readmitted within 30 days due to non-infectious causes. Three patients were readmitted due to culture-negative pneumonia. None had a 14-day re-infection. PCT used to discontinue antibiotics under our ASP did not compromise patients' outcome.

Topics: Aged; Anti-Bacterial Agents; Bacteria; Calcitonin; Calcitonin Gene-Related Peptide; Drug Therapy; Female; Fever of Unknown Origin; Humans; Leukocytosis; Male; Protein Precursors; Recurrence; Sepsis; Treatment Outcome

The aim of the study was to evaluate the impact of procalcitonin (PCT) measurement on antibiotic use in children with fever without source.. Children aged 1 to 36 months presenting to a pediatric emergency department (ED) with fever and no identified source of infection were eligible to be included in a randomized controlled trial. Patients were randomly assigned to 1 of 2 groups as follows: PCT+ (result revealed to the attending physician) and PCT- (result not revealed). Patients from both groups also had complete blood count, blood culture, urine analysis, and culture performed. Chest radiography or lumbar puncture could be performed if required.. Of the 384 children enrolled and equally randomized into the PCT+ and PCT- groups, 62 (16%) were diagnosed with a serious bacterial infection (urinary tract infection, pneumonia, occult bacteremia, or bacterial meningitis) by primary ED investigation. Ten were also found to be neutropenic (<500 x 10(6)/L). Of the remaining undiagnosed patients, 14 (9%) of 158 received antibiotics in the PCT+ group vs 16 (10%) of 154 in the PCT- group (Delta -2%; 95% confidence interval [CI], -8 to 5). A strategy to treat all patients with PCT of 0.5 ng/mL or greater with prophylactic antibiotic in this group of patients would have resulted in an increase in antibiotic use by 24% (95% CI, 15-33).. Semiquantitative PCT measurement had no impact on antibiotic use in children aged 1 to 36 months who presented with fever without source. However, a strategy to use prophylactic antibiotics in all patients with abnormal PCT results would have resulted in an increase use of antibiotics.

Topics: Anti-Bacterial Agents; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Cohort Studies; Emergency Service, Hospital; Fever of Unknown Origin; Hospitalization; Humans; Infant; Predictive Value of Tests; Protein Precursors; Reproducibility of Results; Treatment Outcome

In order to assess the diagnostic value of procalcitonin, 158 patients with febrile neutropenia from centres across Europe were studied. Patients with fever were diagnosed on the basis of either: (1) clinical, radiological and microbiological criteria; or (2) the procalcitonin value. In the latter case, concentrations of 0.5-1.0 ng/mL were considered diagnostic of localised infection, concentrations of 1.0-5.0 ng/mL of bacteraemia, and concentrations of > 5.0 ng/mL of severe sepsis. Procalcitonin and C-reactive protein were estimated daily in serum by immunochemiluminescence and nephelometry, respectively. Overall, the sensitivity (specificity) of procalcitonin for bacteraemia was 44.2% (64.3%) at concentrations of 1.0-5.0 ng/mL, and 83.3% (100%) for severe sepsis at concentrations of > 5.0 ng/mL. It was concluded that procalcitonin is a marker strongly suggestive of severe sepsis at concentrations of > 5.0 ng/mL. Estimated concentrations of < 0.5 ng/mL indicate that infection is unlikely, but it was observed that bacteraemia associated with coagulase-negative staphylococci may fail to elevate serum procalcitonin levels.

Topics: Adult; Aged; Bacteremia; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever of Unknown Origin; Gram-Negative Bacteria; Gram-Positive Cocci; Humans; Male; Middle Aged; Neutropenia; Protein Precursors; Sensitivity and Specificity

Does procalcitonin (PCT) allow differentiation between infection and rejection following liver transplantation in the case of fever of unknown origin (FUO)?. Open prospective trial.. transplant intensive care unit at a university hospital.. Forty patients after liver transplantation.. Liver biopsy for diagnosis of rejection, transcutaneous aspiration cytology for monitoring of lymphocyte activation.. Procalcitonin from EDTA plasma, APACHE II, Sepsis, score (Elbute and Stoner).. Eleven patients suffered an infectious complication resulting in an increase in PCT levels (2.2-41.7 ng/ml). Eleven patients developed a rejection episode; none of these patients showed a rise in PCT levels. The statistical difference between PCT levels in rejection and infection was significant (p<0.05) on the day of diagnosis.. PCT allows differentiation between rejection and infection in the case of FUO. Elevation of PCT plasma levels develops early postoperatively due to operation trauma, and, in the case of FUO with no rise in PCT, a rejection may be suspected.

Topics: Analysis of Variance; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Fever of Unknown Origin; Graft Rejection; Humans; Liver Transplantation; Male; Postoperative Complications; Prospective Studies; Protein Precursors; Reproducibility of Results; Sensitivity and Specificity; Sepsis

Parents frequently bring their children to the Emergency Department (ED) because of the fever without apparent source (FWAS). To avoid possible complications, it is important to recognize serious bacterial infection (SBI) as early as possible. Various tests, including different clinical scores and scales, are used in the laboratory evaluation of patients. However, it is still impossible to predict the presence of SBI with complete certainty. Galetto-Lacour et al. developed and validated a risk index score, named Lab-score. Lab-score is based on the three predictive variables independently associated with SBI: procalcitonin (PCT), C-reactive protein (CRP), and urinary dipstick. The objective of this study was to assess the performance of the Lab-score in predicting SBI in well-appearing infants ≤ 180 days of age with FWAS, who presented to ED and were hospitalized with suspicion of having SBI. Based on this study findings, white blood cells count (WBC), CRP, PCT, and lab-score ≥ 3 were confirmed as useful biomarkers for differentiation between SBI and non-SBI. Also, receiver operating characteristic curve (ROC) analysis confirmed that all of them were useful for differentiation between SBI and non-SBI patients with the highest area under curve (AUC) calculated for the Lab-score. The results of this research confirmed its value, with calculated sensitivity of 67.7% and specificity of 98.6% in prediction of SBI in infants aged ≤ 180 days. Its value was even better in infants aged ≤ 90 days with sensitivity of 75% and specificity of 97.7%. In conclusion, we demonstrated the high value of lab-score in detecting SBI in infants under 6 months of age with FWAS.

Topics: Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Croatia; Early Diagnosis; Emergency Service, Hospital; Female; Fever of Unknown Origin; Hospitalization; Humans; Infant; Infant, Newborn; Male; Patient Admission; Prevalence; Prognosis; Protein Precursors; Reproducibility of Results; Sensitivity and Specificity

Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers.. A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted.. This study included 121 patients ≥18 years old diagnosed with "classical FUO" (axillary temperature ≥38.0°C at least twice over a ≥3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011.. The causative disease was infectious diseases in 28 patients (23.1%), non-infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of <4,000/μL than for a WBC count of 4,000-8,000/μL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of >40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease.. The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Sedimentation; Body Temperature; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Fever of Unknown Origin; Humans; Infections; Inflammation; Japan; Leukocyte Count; Male; Middle Aged; Neoplasms; Predictive Value of Tests; Protein Precursors; Retrospective Studies

Much effort has been put in the past years to create and assess accurate tools for the management of febrile infants. However, no optimal strategy has been so far identified. A sequential approach evaluating, first, the appearance of the infant, second, the age and result of the urinanalysis and, finally, the results of the blood biomarkers, including procalcitonin, may better identify low risk febrile infants suitable for outpatient management.. To assess the value of a sequential approach ('step by step') to febrile young infants in order to identify patients at a low risk for invasive bacterial infections (IBI) who are suitable for outpatient management and compare it with other previously described strategies such as the Rochester criteria and the Lab-score.. A retrospective comparison of three different approaches (step by step, Lab-score and Rochester criteria) was carried out in 1123 febrile infants less than 3 months of age attended in seven European paediatric emergency departments. IBI was defined as isolation of a bacterial pathogen from the blood or cerebrospinal fluid.. Of the 1123 infants (IBI 48; 4.2%), 488 (43.4%) were classified as low-risk criteria according to the step by step approach (vs 693 (61.7%) with the Lab-score and 458 (40.7%) with the Rochester criteria). The prevalence of IBI in the low-risk criteria patients was 0.2% (95% CI 0% to 0.6%) using the step by step approach; 0.7% (95% CI 0.1% to 1.3%) using the Lab-score; and 1.1% (95% CI 0.1% to 2%) using the Rochester criteria. Using the step by step approach, one patient with IBI was not correctly classified (2.0%, 95% CI 0% to 6.12%) versus five using the Lab-score or Rochester criteria (10.4%, 95% CI 1.76% to 19.04%).. A sequential approach to young febrile infants based on clinical and laboratory parameters, including procalcitonin, identifies better patients more suitable for outpatient management.

Topics: Age Factors; Ambulatory Care; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever of Unknown Origin; Humans; Infant; Male; Patient Selection; Protein Precursors; Retrospective Studies; Risk; Sensitivity and Specificity; Urinalysis

The purpose of the study was to evaluate clinical value of dual-phase 18F-FDG SPECT with serum procalcitonin (PCT) in identifying cancers in patients with fever of unknown origin (FUO).. PCT test and dual-phase 18F-FDG SPECT were sequentially performed on 50 consecutive patients with FUO. Two radiologists evaluated all 18F-FDG SPECT data independently. A consensus was reached if any difference of opinions existed. Final diagnosis was based on a comprehensive analysis of results for the PCT test, dual- phase 18F-FDG SPECT and bacterial cultivation, regarded as a gold standard.. Among 50 patients, 34 demonstrated PCT ≥ 0.5 μg/L. Coincidence imaging showed in 37 patients with inflammatory lesions, and 13 with malignancy. Finally, 36 bacterial, 1 fungal and 1 viral infections, as well as 12 cancerous fevers were confirmed by dual-phase 18F-FDG SPECT with PCT, combined with bacterial cultivation and clinical follow-up.. Our study demonstrated that dual-phase 18F-FDG SPECT in association with PCT could be a valuable tool for diagnosis in tumor patients with FUO.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever of Unknown Origin; Fluorodeoxyglucose F18; Follow-Up Studies; Humans; Infections; Male; Middle Aged; Neoplasms; Positron-Emission Tomography; Prognosis; Prospective Studies; Protein Precursors; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Young Adult

Serious bacterial illness (SBI) presents a diagnostic challenge in febrile infants. History, clinical signs, and laboratory information combined with experiential knowledge affects decisions to admit and treat.. To assess the utility of serum procalcitonin and the Acute Infantile Observation Score (AIOS) performed at emergency department presentation in predicting (a) confirmed serious bacterial illness and (b) illness severity.. Sensitivity, specificity, and likelihood ratios were calculated for C-reactive protein, white cell count, serum procalcitonin, and AIOS.. Forty-six infants were recruited. Seven had a diagnosis of SBI, 28 were moderately ill with length of stay >24 hours, and 12 were severely ill with length of stay >96 hours. The positive likelihood ratios for confirmed SBI were C-reactive protein = 5.3, procalcitonin = 0.43, white cell count = 1.9, and AIOS = 1.5.. Procalcitonin and the AIOS do not modify the diagnostic uncertainty of the ED physician assessing the febrile infant with respect to admission or antibiotic treatment above standard laboratory investigations.

Topics: Acute Disease; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Female; Fever of Unknown Origin; Humans; Infant; Infections; Lymphocyte Count; Male; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Severity of Illness Index

Health professionals and researchers have become increasingly interested in biomarkers that help them in diagnosis of infections with recent growing attention to procalcitonin (PCT) and pro-adrenomedullin (proADM).. This study compares proADM to PCT as diagnostic and prognostic biomarkers of infection in febrile patients with hematologic malignancies (HMs). From June 2009 to December 2010, 340 febrile HM patients were evaluated for presence of sepsis, systemic inflammatory response syndrome (SIRS), documented infections, and response to antimicrobial therapy.. ProADM and PCT levels were measured at onset of fever and then on days 4-7 afterward. Of the 340 patients, 103 had definite sepsis, and 159 had SIRS. Only proADM initial levels were significantly higher in patients with localized bacterial infections than in those with no documented infection (P = .019) and in patients with definite sepsis than those with SIRS (P = .023). The initial proADM and PCT levels were significantly higher in neutropenic patients with BSIs than in those without documented infections (P = .010 and P = . 011, respectively). Follow-up, proADM, and PCT levels decreased significantly in response to antimicrobial therapy in patients with bacterial infections (BSIs or localized; P = .007 and P = .002, respectively).. ProADM and PCT have promising roles in assisting clinicians in managing febrile HM patients. However, proADM appears to have the advantage of predicting localized bacterial infection and differentiating sepsis from SIRS.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Drug Monitoring; Female; Fever of Unknown Origin; Hematologic Neoplasms; Humans; Male; Middle Aged; Protein Precursors; Young Adult

Fever suggests the presence of microbial infection in critically ill patients. The aim was to compare the role of old and new biomarkers in predicting absence or presence of microbial infection, its invasiveness and severity in critically ill patients with new onset fever.. We prospectively studied 101 patients in the intensive care unit with new onset fever (>38.3 °C). Routine infection parameters, lactate, procalcitonin (PCT), midregional pro-adrenomedullin (MR proADM), midregional pro-atrial natriuretic peptide (MR proANP) and copeptin (COP) were measured daily for three days after inclusion. Likelihood, invasiveness (by bloodstream infection, BSI) and severity of microbial infection were assessed by cultures, imaging techniques and clinical courses.. All patients had systemic inflammatory response syndrome; 45% had a probable or proven local infection and 12% a BSI, with 20 and 33% mortality in the ICU, respectively. Only peak PCT (cutoff 0.65 ng/mL at minimum) was of predictive value for all endpoints studied, i.e. BSI, septic shock and mortality (high risk infection) and infection without BSI, shock and mortality (low risk infection), at areas under the receiver operating characteristic curves varying between 0.67 (P = 0.003) and 0.72 (P < 0.001). In multivariable analysis, the combination of C-reactive protein and lactate best predicted high risk infection, followed by PCT. For low risk infection, PCT was the single best predictor.. In critically ill patients with new onset fever, plasma PCT as a single variable, among old and new biomarkers, best helps, to some extent, to predict ICU-acquired, high risk microbial infection when peaking above 0.65 ng/mL and low risk infection when peaking below 0.65 ng/mL.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Fever of Unknown Origin; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Survival Analysis; Systemic Inflammatory Response Syndrome

The reliability of procalcitonin as a predictor of invasive infection in infants <36 months of age with fever and nontoxic appearance was assessed in 868 patients, 15 (1.7%) of whom had invasive infection. The area under the receiver operating characteristic curve for procalcitonin was 0.87 (optimum cutoff 0.9 ng/mL, sensitivity 86.7%, specificity 90.5%), whereas for C-reactive protein it was 0.79 (optimum cutoff 91 mg/L, sensitivity 33.3%, specificity 95.9%). In infants with fever of <8 hours duration, the area under the receiver operating characteristic curve was 0.97 for procalcitonin and 0.76 for C-reactive protein. Procalcitonin was a useful biomarker to predict invasive infection in non-toxic-appearing infants with fever without apparent focus, particularly in febrile episodes of <8 hours duration.

Topics: Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Emergency Medical Services; Female; Fever of Unknown Origin; Humans; Infant; Male; Meningitis, Bacterial; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

The "Lab-score" combining C-reactive protein, procalcitonin and urine dipstick results has recently been derived and validated as an accurate tool for predicting severe bacterial infections (SBIs) in children with fever without source. We aimed to assess the Lab-score usefulness in predicting SBI, especially invasive bacterial infections (IBIs), in well-appearing infants <3 months with fever without source.. A multicenter retrospective study was conducted in 7 pediatric emergency departments in Spain and Italy. An SBI was defined as isolation of a bacterial pathogen from urine, blood, cerebrospinal fluid or stools, an IBI as isolation of a bacterial pathogen from blood or cerebrospinal fluid. The diagnostic characteristics of the Lab-score for detection of SBI and IBI were calculated.. An SBI was diagnosed in 287 (28.3%) of 1012 patients and an IBI in 23 (2.1%) of 1098. The positive and negative likelihood ratios of a score ≥3 for SBI prediction were 10.2 (95% confidence interval [CI]: 9.5-10.9) and 0.5 (95% CI: 0.5-0.5), respectively. The area under the receiver operating characteristic curve was 0.83 (95% CI: 0.80-0.86). The same diagnostic accuracy measures for identification of IBI were 4.3 (95% CI: 4-4.6), 0.4 (95% CI: 0.3-0.5) and 0.85 (95% CI: 0.76-0.94), respectively. Use of Lab-score would have resulted in misdiagnosis of 7 (30%) infants with IBI.. In well-appearing infants with fever without source, the Lab-score seems a more useful tool for ruling in, rather than ruling out, SBI. Its accuracy for IBI prediction was unsatisfactory.

Topics: Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnostic Techniques and Procedures; Female; Fever of Unknown Origin; Humans; Infant; Infant, Newborn; Italy; Male; Protein Precursors; Retrospective Studies; Severity of Illness Index; Spain; Urine

The purpose of this study was to explore the diagnostic value of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), procalcitonin (PCT), and C-reactive protein (CRP) serum levels for differentiating sepsis from SIRS, identifying new fever caused by bacteremia, and assessing prognosis when new fever occurred.. We enrolled 144 intensive care unit (ICU) patients: 60 with systemic inflammatory response syndrome (SIRS) and 84 with sepsis complicated by new fever at more than 48 h after ICU admission. Serum sTREM-1, PCT, and CRP levels were measured on the day of admission and at the occurrence of new fever (>38.3°C) during hospitalization. Based on the blood culture results, the patients were divided into a blood culture-positive bacteremia group (33 patients) and blood culture-negative group (51 patients). Based on 28-day survival, all patients, both blood culture-positive and -negative, were further divided into survivor and nonsurvivor groups.. On ICU day 1, the sepsis group had higher serum sTREM-1, PCT, and CRP levels compared with the SIRS group (P <0.05). The areas under the curve (AUC) for these indicators were 0.868 (95% CI, 0.798-0.938), 0.729 (95% CI, 0.637-0.821), and 0.679 (95% CI, 0.578-0.771), respectively. With 108.9 pg/ml as the cut-off point for serum sTREM-1, sensitivity was 0.83 and specificity was 0.81. There was no statistically significant difference in serum sTREM-1 or PCT levels between the blood culture-positive and -negative bacteremia groups with ICU-acquired new fever. However, the nonsurvivors in the blood culture-positive bacteremia group had higher levels of serum sTREM-1 and PCT (P <0.05), with a prognostic AUC for serum sTREM-1 of 0.868 (95% CI, 0.740-0.997).. Serum sTREM-1, PCT, and CRP levels each have a role in the early diagnosis of sepsis. Serum sTREM-1, with the highest sensitivity and specificity of all indicators studied, is especially notable. sTREM-1, PCT, and CRP levels are of no use in determining new fever caused by bacteremia in ICU patients, but sTREM-1 levels reflect the prognosis of bacteremia.. ClinicalTrial.gov identifier NCT01410578.

Topics: Adult; Aged; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Clinical Laboratory Techniques; Cohort Studies; Diagnosis, Differential; Female; Fever of Unknown Origin; Humans; Intensive Care Units; Male; Membrane Glycoproteins; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Receptors, Immunologic; Sensitivity and Specificity; Serum; Triggering Receptor Expressed on Myeloid Cells-1

Procalcitonin (PCT) has been introduced in many European protocols for the management of febrile children. Its value among young, well-appearing infants, however, is not completely defined. Our objective was to assess its performance in diagnosing serious bacterial infections and specifically invasive bacterial infections (IBIs) in well-appearing infants aged <3 months with fever without source (FWS).. Well-appearing infants aged <3 months with FWS admitted to 7 European pediatric emergency departments were retrospectively included. IBI was defined as the isolation of a bacterial pathogen in blood or cerebrospinal fluid culture.. We included 1112 infants who had PCT measured and a blood culture performed. IBI was diagnosed in 23 cases (2.1%). In the multivariate analysis including clinical and laboratory data, PCT was the only independent risk factor for IBI (odds ratio 21.69; 95% confidence interval [CI] 7.93-59.28 for PCT ≥ 0.5 ng/mL). Positive likelihood ratios for PCT ≥ 2 ng/mL and C-reactive protein (CRP) >40 mg/L were 11.14 (95% CI 7.81-15.89) and 3.45 (95% CI 2.20-5.42), respectively. Negative likelihood ratios for PCT <0.5 ng/mL and CRP <20 mg/L were 0.25 (95% CI 0.12-0.55) and 0.41 (95% CI 0.22-0.76). Among patients with normal urine dipstick results and fever of recent onset, areas under the receiver operator characteristic curve for PCT and CRP were 0.819 and 0.563, respectively.. Among well-appearing young infants with FWS, PCT performs better than CRP in identifying patients with IBIs and seems to be the best marker for ruling out IBIs. Among patients with normal urine dipstick results and fever of recent onset, PCT remains the most accurate blood test.

Topics: Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever of Unknown Origin; Humans; Infant; Infant, Newborn; Male; Protein Precursors; Retrospective Studies

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cord Blood Stem Cell Transplantation; Diagnostic Tests, Routine; Fever of Unknown Origin; Humans; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Protein Precursors; Radiography, Thoracic; Serum; Tomography, X-Ray Computed; Tuberculosis

To compare semi-quantitative procalcitonin with C-reactive protein in predicting bacteraemia in haematological patients with neutropenic fever.. A total of 77 patients treated with intensive chemotherapy for haematological malignancy at Kuopio University Hospital were candidates for study entry. Eleven of these patients did not fulfil the criteria for neutropenic fever, and 66 patients were finally included. Nineteen patients had acute myeloid leukaemia and 47 had received high-dose chemotherapy supported by autologous stem cell transplant. Ninety neutropenic fever episodes in these 66 patients fulfilled the study entry criteria, with microbiological cultures, procalcitonin and C-reactive protein measurements available. Serum procalcitonin and C-reactive protein were analyzed at the onset of each neutropenic fever episode on day 0, and then daily from days 1 to 4.. Bacteraemia was observed in 21 episodes (23%) and the criteria for severe sepsis were fulfilled in 13 episodes (14%). Half of the bacteraemic episodes were caused by Gram-negative bacteria. The kinetics of procalcitonin and C-reactive protein were similar, with increasing levels for 2 to 4 days after the onset of fever. The procalcitonin level on days 1, 2, 3 and 4 was associated with bacteraemia and Gram-negative bacteraemia, but not with the development of severe sepsis. On day 1, a procalcitonin level above 0.5 ng/ml had a sensitivity of 57% and 70% and specificity of 81% and 77% to predict bacteraemia and Gram-negative bacteraemia, respectively.. An elevated level of procalcitonin within 24 h after the onset of neutropenic fever predicts bacteraemia and Gram-negative bacteraemia in haematological patients.

Topics: Adolescent; Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever of Unknown Origin; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis; Time Factors; Young Adult

Procalcitonin (PCT) is a current, frequently used marker for severe bacterial infection. The aim of this study was to assess the ability of PCT levels to differentiate bacteremic from nonbacteremic patients with fever. We assessed whether PCT level could be used to accurately rule out a diagnosis of bacteremia.. Serum samples and blood culture were obtained from patients with fever between August 2008 and April 2009. PCT was analyzed using a VIDAS® B.R.A.H.M.S PCT assay. We reviewed the final diagnosis and patient histories, including clinical presentation and antibiotic treatment.. A total of 300 patients with fevers were enrolled in this study: 58 with bacteremia (positive blood culture) (group I); 137 with local infection (group II); 90 with other diseases (group III); and 15 with fevers of unknown origin (group IV). PCT levels were significantly higher in patients with bacteremia than in those with non-bacteremia (11.9 ± 25.1 and 2.5 ± 14.7 ng/mL, respectively, p < 0.001). The sensitivity and specificity were 74.2% and 70.1%, respectively, at a cut-off value of 0.5 ng/mL. A serum PCT level of < 0.4 ng/mL accurately rules out diagnosis of bacteremia.. In febrile patients, elevated PCT may help predict bacteremia; furthermore, low PCT levels were helpful for ruling out bacteremia as a diagnosis. Therefore, PCT assessment could help physicians limit the number of prescriptions for antibiotics.

Topics: Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Female; Fever; Fever of Unknown Origin; Humans; Male; Middle Aged; Protein Precursors; Sensitivity and Specificity; Young Adult

No sensitive, specific marker able to discriminate favourable or unfavourable outcome of fever of unknown origin (FUO) at diagnosis has been identified. Procalcitonin, a recently assessed infection marker, may be useful in predicting the outcome of FUO.. We conducted a prospective study examining the following variables: age 0.5-22 years; solid tumour diagnosis; chemotherapy-related grade-4 febrile neutropenia (FN). A complete clinical, bacteriological and biological evaluation was performed at hospital admission (H0). Other investigations depended on clinical status. FUO was considered to be of unfavourable outcome if the fever was persistent or re-appeared at day 3 (or later), or if secondary clinical or microbiological infection occurred. To validate the results of the analysis the data set was randomly split into a training set and a validation set.. Out of 172 episodes of FN, 136 episodes were classified as FUO (80%). Seventy-two (53%) were included in this study. PCT values were significantly higher in episodes of unfavourable outcome (P < 0.001). None of the other prediction candidates appeared to be significantly linked to the risk of unfavourable outcome. In the validation set, the best PCT cut-off was 0.12 micro/L, which was associated with a sensitivity of 80% and specificity of 64%.. PCT-H0 level can predict FUO outcome. A protocol based on PCT-H0 measurement, integrating clinical and bacteriological evaluation, facilitates shorter hospital stays and less antibiotic treatment. Patients with a PCT-H0 value <0.12 micro/L could benefit from an outpatient treatment starting at H48 thus reducing hospitalisation costs and improving quality of life.

Topics: Adolescent; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Fever of Unknown Origin; Humans; Infant; Logistic Models; Male; Neoplasms; Neutropenia; Prospective Studies; Protein Precursors; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Young Adult

Circulating nucleic acids were discovered more than 60 y ago. With the recent developments in the study of circulating nucleic acids, its application in the diagnostic field has increased. The objective of this study was to assess the usefulness of the quantification of cell-free plasma DNA (CF-DNA) concentration in the diagnosis of infections in febrile patients and as a prognostic marker in septic patients.. Concentrations of CF-DNA, procalcitonin (PCT) and C-reactive protein (CRP) were measured in 110 febrile patients who were clinically diagnosed with fever of unknown origin, localized infection, sepsis or septic shock.. Concentrations of CF-DNA increase according to the severity of the infection. The best cut-off point for predicting infection was 2800 GE (genome equivalents)/mL (sensitivity: 95.0%; specificity: 96.7%) and 14,000 GE/mL for sepsis prediction (sensitivity: 77.8%; specificity: 94.6%). Higher concentrations of CF-DNA were found in exitus septic patients than in survivors. The diagnostic efficiency of CF-DNA was similar to PCT and higher than CRP in infectious processes.. Normal concentrations of CF-DNA can exclude the presence of an infection in febrile patients, and very high concentrations (>10-fold over the normal reference range) stratify the severity of infections, showing a high prognostic value to predict mortality in the absence of other causes for elevated CF-DNA.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; DNA; Female; Fever of Unknown Origin; Humans; Male; Middle Aged; Protein Precursors; Seizures, Febrile; Sepsis; Shock, Septic; Young Adult

To evaluate potential markers of serious bacterial infection (SBI) in infants under 3 months of age presenting with fever of unknown origin.. We retrospectively studied all infants under 3 months of age seen in the emergency department between January 2004 and December 2006 for a febrile syndrome with no identifiable focus. Clinical data, procalcitonin (PCT), C reactive protein (CRP) and leucocyte count were evaluated for their ability to discriminate between SBI and non-SBI; receiver operating characteristic (ROC) curves were constructed for the laboratory markers and analysis was performed by multivariate logistic regression.. The sample comprised 347 patients (23.63% with SBI). Mean PCT, CRP, leucocyte and neutrophil count were significantly higher in the group with SBI unlike the other criteria studied. The area under the ROC curve (AUC) for PCT was 0.77 (95% CI 0.72 to 0.81) and 0.79 for CRP (95% CI 0.75 to 0.84); both these variables were stronger predictors than leucocyte count (0.67, 95% CI 0.63 to 0.73). In the 15 infants with more invasive bacterial infections (sepsis, bacteraemia, bacterial meningitis), the diagnostic value of PCT (AUC 0.84, 95% CI 0.79 to 0.88) was higher than CRP (AUC 0.68, 95% CI 0.63 to 0.73). In infants who had been febrile for under 12 h, the differences between PCT, CRP and leucocyte count were statistically significant in both SBI and non-SBI groups, with increasing predictive value of PCT and decreasing value of CRP.. PCT, CRP, and leucocyte count have intrinsic predictive value for SBI in febrile infants under 3 months of age. The diagnostic value of PCT is greater than CRP for more invasive bacterial infections and for fever of short duration.

Topics: Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Emergency Service, Hospital; Female; Fever of Unknown Origin; Humans; Infant; Infant, Newborn; Leukocyte Count; Logistic Models; Male; Predictive Value of Tests; Protein Precursors; Retrospective Studies; ROC Curve; Spain

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%.

Topics: Bacteria; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Fever of Unknown Origin; Humans; Infant; Infant, Newborn; Leukocyte Count; Protein Precursors; Sensitivity and Specificity; Urinalysis

Severe sepsis is not clinically apparent during the first 24 hours of hospitalization in most children with cancer and febrile neutropenia (FN), delaying targeted interventions that could impact mortality. The aim of this study was to prospectively evaluate biomarkers obtained within 24 hours of hospitalization as predictors of severe sepsis before it becomes clinically evident.. Children with cancer, admitted with FN at high risk for an invasive bacterial infection in 6 public hospitals in Santiago, Chile, were monitored throughout their clinical course for occurrence of severe sepsis. Clinical, demographic and 6 biomarkers [eg, blood urea nitrogen, serum glucose, lactic dehydrogenase, serum C-reactive protein (CRP), interleukin (IL)-8, and procalcitonin] were obtained at the time of admission and after 24 hours. Biomarkers independently associated with severe sepsis diagnosed after the first 24 hours of hospitalization were identified by logistic regression analysis.. A total of 601 high risk FN episodes were enrolled between June 2004 and October 2006; 151 (25%) developed severe sepsis of which 116 (77%) were not clinically apparent during the first 24 hours of hospitalization. Risk factors for severe sepsis were age > or =12 years [odds ratio (OR): 3.85; 95% confidence interval (CI): 2.41-6.15], admission CRP > or =90 mg/L (OR: 2.03; 95% CI: 1.32-3.14), admission IL-8 > or =200 pg/mL (OR: 2.39; 95% CI: 1.51-3.78), 24-hour CRP > or =100 mg/L (OR: 3.06; 95% CI: 1.94-4.85), and 24-hour IL-8 > or =300 pg/mL (OR: 3.13; 95% CI 1.92-5.08).. Age > or =12 years and admission or 24-hour values of CRP > or =90/100 mg/L and IL-8 > or =200/300 pg/mL are predictors of sepsis not clinically apparent during the first 24 hours of hospitalization.

Topics: Adolescent; Age Factors; Biomarkers; Blood Glucose; Blood Urea Nitrogen; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Chile; Female; Fever of Unknown Origin; Hospitalization; Humans; Interleukin-8; L-Lactate Dehydrogenase; Logistic Models; Male; Neoplasms; Neutropenia; Prospective Studies; Protein Precursors; Sepsis

To assess the value of procalcitonin (PCT) and C-reactive protein (CRP), compared with that of total white-blood cell count (WBC) and absolute neutrophil count (ANC), in predicting severe bacterial infections (SBIs) in febrile children admitted to Emergency Department.. A prospective study was conducted in 408 children aged 7-days to 36-months, admitted with fever without source, at a tertiary care Pediatric Emergency Department. PCT, CRP, WBC, and ANC were determined upon admission and compared. Specificity, sensitivity, multilevel likelihood ratios, receiver operating characteristic (ROC) analysis, and multivariate stepwise logistic regression were carried out.. SBI was diagnosed in 94 children (23.1%). PCT, CRP, WBC, and ANC were significantly higher in this group than in non-SBI patients. The area under the ROC (AUC) obtained was 0.82 (95% CI: 0.78-0.86) for PCT, 0.85 (95% CI: 0.81-0.88) for CRP (P = 0.358), 0.71 (95% CI: 0.66-0.75) for WBC, and 0.74 (95% CI: 0.70-0.78) for ANC. Only PCT (OR: 1.32; 95% CI: 1.11-1.57; P < 0.001) and CRP (OR: 1.02; 95% CI: 1.01-1.03; P < 0.001) were retained as significant predictors of SBI in a multiple regression model. For infants with fever <8 hours (n = 45), AUC for PCT and CRP were 0.92 (95% CI: 0.80-0.98) and 0.75 (95% CI: 0.60-0.87), respectively (P = 0.056).. Both PCT and CRP are valuable markers in predicting SBI in children with fever without source and they perform better than WBC and ANC. PCT appears more accurate at the beginning of infections, but overall CRP may be the most convenient marker for its better sensitivity and feasibility.

Topics: Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Emergency Service, Hospital; Female; Fever of Unknown Origin; Humans; Infant; Infant, Newborn; Leukocyte Count; Logistic Models; Male; Multivariate Analysis; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity

The main causes of complications of allogenic hematopoietic stem cell transplantation are infections and graft versus host disease.. To assess the predictive value of C reactive protein (CRP) and procalcitonin (PCT) in the diagnosis of invasive bacterial infections in children with febrile neutropenia after an allogenic hematopoietic stem cell transplantation.. Prospective follow up of patients aged 18 years or less, with febrile neutropenia after an allogenic hematopoietic stem cell transplantation. In all patients, cultures from sterile sites, CRP and PCT determinations were done. CRP levels were also measured prior to transplantation and three times per week for 30 days after the procedure. An independent evaluator, blinded to the results of CRP and PCT, classified children as with or without invasive bacterial infection.. Thirty three patients aged 9+/-5 years (21 males) were studied. Eight had an invasive bacterial infection. Sensitivity, specificity, positive and negative predictive values of a CRP > or = 90 mg/L for the diagnosis of invasive bacterial infection were 25, 80, 29 and 77%, respectively. The figures for a PCT > or = 0.7 ng/ml were 43, 78, 38 and 82%, respectively. No differences in repeated CRP values measured during evolution, were observed.. A CRP > or = 90 mg/L or a PCT > or = 0.7 ng/ml had a high specificity and negative predictive value but low sensitivity for the diagnosis of invasive bacterial infections in recipients of allogenic hematopoietic stem cell transplantation.

Topics: Adolescent; Anti-Infective Agents; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Fever of Unknown Origin; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infant, Newborn; Male; Neutropenia; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic

Topics: Adolescent; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Fever of Unknown Origin; Humans; Infant; Interleukin-6; Male; Neoplasms; Neutropenia; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Statistics, Nonparametric

Classical markers of infection cannot differentiate reliably between inflammation and infection after neurosurgery. This study investigated the dynamics of serum procalcitonin (PCT) in patients following major neurosurgery. PCT concentrations remained < 0.2 ng/mL during the post-operative course. In contrast, leukocyte and neutrophil counts, as well as C-reactive protein (CRP) levels, increased significantly post-operatively (leukocytes, range 7.1-23.7 x 10(9)/L, p < 0.001; neutrophils, range 70.8-94.5%, p < 0.001; CRP, median 14 mg/L, range 3-95 mg/L, p < 0.001). Analysis of PCT levels using assays with improved sensitivity may be useful in the diagnosis of neurosurgical patients with post-operative fever of unknown origin.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever of Unknown Origin; Humans; Male; Middle Aged; Neurosurgery; Neurosurgical Procedures; Protein Precursors; Reagent Kits, Diagnostic

Procalcitonin (PCT) is a potentially useful marker in pediatric Emergency Departments (ED). The basic objectives of this study were to assess the diagnostic performance of PCT for distinguishing between viral and bacterial infections and for the early detection of invasive bacterial infections in febrile children between 1 and 36 months old comparing it with C-reactive protein (CRP) and to evaluate the utility of a qualitative rapid test for PCT in ED.. Prospective, observational and multicenter study that included 445 children who were treated for fever in pediatric ED. Quantitative and qualitative plasma values of PCT and CRP were correlated with the final diagnosis. To obtain the qualitative level of PCT the BRAHMS PCT-Q rapid test was used.. Mean PCT and CRP values in viral infections were 0.26 ng/ml and 15.5 mg/l, respectively. The area under the curve obtained for PCT in distinguishing between viral and bacterial infections was 0.82 (sensitivity, 65.5%; specificity, 94.3%; optimum cutoff, 0.53 ng/ml), whereas for CRP it was 0.78 (sensitivity, 63.5%; specificity, 84.2%; optimum cutoff, 27.5 mg/l). PCT and CRP values in invasive infections (PCT, 24.3 ng/ml; CRP 96.5 mg/l) were significantly higher than those for noninvasive infections (PCT, 0.32 ng/ml; CRP, 23.4 mg/l). The area under the curve for PCT was 0.95 (sensitivity, 91.3%; specificity, 93.5%; optimum cutoff, 0.59 ng/ml), significantly higher (P < 0.001) than that obtained for CRP (0.81). The optimum cutoff value for CRP was >27.5 mg/l with sensitivity and specificity of 78 and 75%, respectively. In infants in whom the evolution of fever was <12 h (n = 104), the diagnostic performance of PCT was also greater than that of CRP (area under the curve, 0.93 for PCT and 0.69 for CRP; P < 0.001). A good correlation between the quantitative values for PCT and the PCT-Q test was obtained in 87% of cases (kappa index, 0.8). The sensitivity of the PCT-Q test (cutoff >0.5 ng/ml) for detecting invasive infections and differentiating them from noninvasive infections was 90.6%, with a specificity of 83.6%.. PCT offers better specificity than CRP for differentiating between the viral and bacterial etiology of the fever with similar sensitivity. PCT offers better sensibility and specificity than CRP to differentiate between invasive and noninvasive infection. PCT is confirmed as an excellent marker in detecting invasive infections in ED and can even make early detection possible of invasive infections if the evolution of the fever is <12 h. The PCT-Q test has a good correlation with the quantitative values of the marker.

Topics: Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Critical Illness; Diagnosis, Differential; Emergency Service, Hospital; Female; Fever of Unknown Origin; Hospitals, Pediatric; Humans; Infant; Infant, Newborn; Male; Predictive Value of Tests; Probability; Protein Precursors; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Viremia

Procalcitonin (PCT) is an established marker for severe systemic bacterial infection and sepsis. So far the relevance of PCT in healthy individuals or patients with local infections is unclear due to the lack of highly sensitive assays. The aim of our study was the characterization of a new sensitive PCT assay, the establishment of reference values and the assessment of diagnostic accuracy.. We assessed PCT values in 522 patients with different infectious and non infectious conditions and 410 healthy controls by a new coated tube sandwich chemiluminescence assay B.R.A.H.M.S ProCa-S (2 step assay, time to result 2.5 hours).. The lower detection limit was 6.0 ng/L, with a functional assay sensitivity below 7 ng/L. Samples above 250 ng/L gave excellent correlation to the LUMItest PCT (r = 0.98, p < 0.0001). There was no high dose hook effect up to a concentration of 21,300 ng/L. The 410 healthy controls had a median concentration of 12.7 ng/L (95% CI: 12.6-14.7 ng/L). 65 controls had non-detectable PCT values (defined as 5 ng/L). The 2.5th percentile of the normal population was 5 ng/L and the 97.5th percentile was 46.7 ng/L. ROC plot analysis resulted in an area under the curve (AUC) of 0.90. The optimal decision threshold was at 50 ng/L, with a sensitivity for infection of 77.8% and a specificity of 98.5% (positive predictive value 97.7%, negative predictive value 84.9%). There was a highly significant (p < 0.0001) difference in the PCT median between healthy individuals and patients with infections (e.g. pneumonia, peritonitis) but not non-infectious controls (e.g. pregnancy, autoimmune disease).. The new PCT assay is 30 times more sensitive than the established routine assay LUMItest PCT, thus allowing for the first time PCT detection in healthy individuals. First results indicate that the assay is suitable to differentiate local bacterial infections from other non-infectious diseases.

Topics: Adult; Appendicitis; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever of Unknown Origin; Humans; Infections; Luminescent Measurements; Lung Diseases; Male; Middle Aged; Pregnancy; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Reference Values; Reproducibility of Results; Respiratory Distress Syndrome; Sensitivity and Specificity

The ability of measurement of serum procalcitonin (PCT) levels to differentiate bacteremic from nonbacteremic infectious episodes in patients hospitalized for community-acquired infections was assessed. Serum samples were obtained from adult inpatients with fever to determine the serum PCT level, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). Of 165 patients, 22 (13%) had bacteremic episodes and 143 (87%) had nonbacteremic episodes. PCT levels, CRP levels, and ESRs were significantly higher in bacteremic patients than in nonbacteremic patients (P<.001,.007, and.024, respectively). The best cutoff value for PCT was 0.4 ng/mL, which was associated with a negative predictive value of 98.8%. Area under the receiver operating characteristic curve was 0.83 for PCT, which was significantly higher than that for CRP (0.68; P<.0001) and ESR (0.65; P<.05). A serum PCT level of <0.4 ng/mL accurately rules out the diagnosis of bacteremia. The use of PCT assessment could help physicians limit the number of blood cultures to be processed and the number of antibiotic prescriptions.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Diagnosis, Differential; Female; Fever; Fever of Unknown Origin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Diagnostic Errors; Fever of Unknown Origin; Graft Rejection; Humans; Infections; Liver Transplantation; Muromonab-CD3; Protein Precursors; Tumor Necrosis Factor-alpha

Does procalcitonin (PCT) differentiate between infection and rejection after liver transplantation in patients with fever of unknown origin?. Open prospective trial.. Transplant intensive care unit at a university hospital.. Forty patients after liver transplantation.. Liver biopsy for the diagnosis of rejection and transcutaneous aspiration cytology for monitoring of lymphocyte activation.. Procalcitonin from EDTA plasma, Acute Physiology and Chronic Health Evaluation II, and sepsis score.. Eleven patients experienced an infectious complication resulting in an increase in PCT concentrations (2.2-41.7 ng/mL). Eleven patients had a rejection episode; none of these patients showed a rise in PCT concentrations. The statistical difference between PCT concentrations in rejection and infection was significant (p<.05) on the day of diagnosis.. PCT allows for differentiation between rejection and infection in patients with fever of unknown origin. Elevation of PCT plasma concentrations develops early postoperatively from operation trauma, and in the case of fever of unknown origin, with no rise in PCT, a rejection may be suspected.

Topics: Analysis of Variance; APACHE; Biopsy; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Discriminant Analysis; Fever of Unknown Origin; Graft Rejection; Humans; Infections; Liver Transplantation; Lymphocyte Activation; Monitoring, Physiologic; Prospective Studies; Protein Precursors; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Statistics, Nonparametric; Time Factors

Sensitive parameters of inflammation are rare in neutropenic cancer patients. In this study, procalcitonin (PCT), C-reactive protein (CRP), interleukin 6 (IL-6), IL-8, the soluble IL-2 receptor (sIL-2R) and the soluble tumour necrosis factor receptor II (sTNFRII) were evaluated for their diagnostic relevance in febrile episodes of cancer patients. Plasma or serum levels of these parameters were determined in neutropenic children with febrile episodes (n = 122) classified according to both the kind of infection [60 cases of fever of unknown origin (FUO), 28 cases of localized infection, 13 cases of pneumonia, 20 cases of bacteraemia, one case of fungaemia] and the World Health Organization (WHO) score of chemotherapy-induced mucositis. At baseline and during the febrile episodes, the highest levels of all parameters were observed in cases of gram-negative bacteraemia. However, in FUO and localized infections, low or only slightly elevated median levels of all parameters were documented. The degree of chemotherapy-induced mucositis did not influence the value of any parameter. In comparison with the other inflammatory parameters, PCT (optimum cut-off level 0.5 microg/l) was a more sensitive and more specific parameter in the diagnosis of high-risk (gram-negative bacteraemia) and low-risk (FUO) episodes, as well as in the sequential assessment of all febrile neutropenic episodes.

Topics: Adolescent; Adult; Antigens, CD; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Child; Child, Preschool; Cytokines; Female; Fever; Fever of Unknown Origin; Humans; Infant; Interleukin-6; Interleukin-8; Male; Neoplasms; Neutropenia; Protein Precursors; Receptors, Interleukin-2; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Retrospective Studies; Sensitivity and Specificity

To assess the usefulness of markers of inflammation in distinguishing bacterial infection from severe systemic nonbacterial inflammation, concentrations of procalcitonin, neopterin, endotoxin, tumor necrosis factor, and interleukin-6 were measured in 28 neutropenic patients at the onset of fever and twice thereafter at 4 h intervals. Infection was found in 11 patients, and 17 patients had fever of undetermined origin. The procalcitonin concentration increased rapidly in patients with infection: the response was detectable within 8 h of the onset of fever. Procalcitonin is a specific but not a sensitive marker of infection in patients with neutropenic fever. Its poor sensitivity was related to an absent or delayed response in patients with gram-positive infections. Considerable overlap between infected and noninfected patients was found in levels of endotoxin, tumor necrosis factor, and interleukin-6.

Topics: Adult; Aged; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Endotoxins; Fever of Unknown Origin; Hematologic Neoplasms; Humans; Interleukin-6; Middle Aged; Neopterin; Neutropenia; Protein Precursors; Tumor Necrosis Factor-alpha

We assessed the predictive value of procalcitonin (PCT) serum levels in neutropenic patients with fever and various types of infection, using a prospective 3 times weekly blood sampling protocol during 103 patient episodes. Compared with pre-fever levels, median PCT levels increased after fever onset from 0.16 ng/ml (day -1) to 0.34 ng/ml (day +1). In samples obtained within 32 h after fever onset, PCT levels differed significantly between (clinically or microbiologically) documented infection and unexplained fever (median 0.51 vs. 0.26 ng/ml), between bacteraemia and non-bacteraemic infection (median 0.8 vs. 0.27 ng/ml) and between Gram-negative bacteraemia and all other episodes (median 1.28 vs. 0.31 ng/ml). Receiver-operating-characteristic (ROC) curves indicated that the discriminatory power of PCT was best for predicting bacteraemia vs. non-bacteraemic infection (sensitivity 73%; specificity 86%; area under the ROC curve 0.795; cut-off value 0.5 ng/ml). Compared with interleukin-8 (IL-8) serum levels, test characteristics were similar in the prediction of bacteraemia vs. non-bacteraemic infection and in the prediction of documented infection vs. unexplained fever, while IL-8 was better than PCT in the prediction of Gram-negative bacteraemia (area under the ROC curve 0.965 vs. 0.758).

Topics: Adolescent; Adult; Aged; Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Fever of Unknown Origin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Middle Aged; Neutropenia; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity

Exposure to bacterial endotoxin, perhaps due to bowel congestion or ischaemia and altered gut permeability, may result in immune activation that is characteristic for patients with severe heart failure. It is known that blood procalcitonin rises in response to bacterial endotoxin exposure.. We measured procalcitonin in a group of 29 patients with acute cardiogenic shock and no sign of infection (all without bacteraemia) and 26 with septic shock. Blood was analysed for procalcitonin, interleukin-6, tumour necrosis factor-alpha (TNF-alpha), c-reactive protein (CRP) and neopterin. Patients were managed conventionally in an intensive care unit with no further experimental procedures.. Three cardiogenic (10%) and seven septic shock patients (27%) survived. Most patients with acute heart failure surviving 12 h or more (18 of 20) developed a pyrexia (738.0 degrees C) of unknown origin in the absence of positive cultures, with a rise in procalcitonin (1.4+/-0.8 to 48.0+/-16.2 ng/ml, P<0.001), CRP (76.5+/-16.4 to 154.7+/-22.9 mg/l, P<0.001) and neopterin (20.7+/-3.5 to 41.2+/-6.7 nmol/l, P<0.001). Patients with septic shock had higher initial levels of cytokines, and higher peak levels. Those with heart failure surviving (n=3) and those dying in the first 12 h (n=9) had no rise in cytokine levels. The patients with high procalcitonin had a higher temperature (38.9+/-0.3 vs. 37.3+/-0.23 degrees C, P<0.05), TNF-alpha (43.95+/-9.64 vs. 16.43+/-4.33 pg/ml; P<0.005) and CRP (146.1+/-18.4 vs. 68.2+/-39.6 mg/ml, P<0.005). Peak procalcitonin levels correlated with peak temperature (r=0.74, P<0.001).. Cardiogenic shock causes a pyrexia of unknown origin in patients surviving for 12 h and that is associated with a rise in procalcitonin levels. This lends support to the hypothesis that patients with cardiogenic shock may be being exposed to bacterial endotoxin at a time when bowel wall congestion and or ischaemia is likely to be present.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Translocation; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Endotoxins; Female; Fever of Unknown Origin; Humans; Male; Middle Aged; Protein Precursors; Shock, Cardiogenic; Shock, Septic; Survival Analysis