Showing papers on "Procalcitonin published in 2010"
TL;DR: A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes.
980 citations
TL;DR: Serum ProCT has become useful as a biomarker to assist in the diagnosis of sepsis, as well as related infectious or inflammatory conditions, and it is also a useful monitor of the clinical course and prognosis, and sensitive and specific assays have been developed for its measurement.
Abstract: The worldwide yearly mortality from sepsis is substantial, greater than that of cancer of the lung and breast combined. Moreover, its incidence is increasing, and its response to therapy has not appreciably improved. In this condition, the secretion of procalcitonin (ProCT), the prohormone of calcitonin, is augmented greatly, attaining levels up to thousands of fold of normal. This hypersecretion emanates from multiple tissues throughout the body that are not traditionally viewed as being endocrine. The serum values of ProCT correlate with the severity of sepsis; they recede with its improvement and worsen with exacerbation. Accordingly, as highlighted in this review, serum ProCT has become useful as a biomarker to assist in the diagnosis of sepsis, as well as related infectious or inflammatory conditions. It is also a useful monitor of the clinical course and prognosis, and sensitive and specific assays have been developed for its measurement. Moreover, it has been demonstrated that the administration of ProCT to septic animals greatly increases mortality, and several toxic effects of ProCT have been elucidated by in vitro experimental studies. Antibodies have been developed that neutralize the harmful effects of ProCT, and their use markedly decreases the symptomatology and mortality of animals that harbour a highly virulent sepsis analogous to that occurring in humans. This therapy is facilitated by the long duration of serum ProCT elevation, which allows for a broad window of therapeutic opportunity. An experimental groundwork has been established that suggests a potential applicability of such therapy in septic humans.
254 citations
TL;DR: Initial PCT level accurately predicted blood culture positivity in patients with CAP, and has the potential to reduce the number of drawn blood cultures in the emergency department and to implement a more targeted allocation of limited health-care resources.
248 citations
TL;DR: All new biomarkers were good predictors of short- and long-term all-cause mortality, superior to inflammatory markers, and at least comparable to CRB-65 score.
Abstract: Rationale: Several new biomarkers are related to mortality in community-acquired pneumonia (CAP).Objectives: Aim of this study was to compare new biomarkers for the prediction of short- and long-term all-cause mortality in CAP.Methods: We enrolled 728 patients (59.0 ± 18.2 yr) with CAP. Midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), proarginin-vasopressin (copeptin), proendothelin-1 (CT-proET-1), procalcitonin (PCT), C-reactive protein, white blood cell (WBC) count, and clinical confusion, respiratory rate, blood pressure, and age over 65 years (CRB-65) score were determined on admission. Patients were followed up for 180 days.Measurements and Main Results: In patients who died of any cause within 28 and 180 days (2.5 and 5.1%, respectively), MR-proADM, MR-proANP, copeptin, CT-proET-1 and PCT as well as CRB-65 were significantly higher compared with survivors. MR-proADM had the best performance for 28 days (HR 3.67) and 180 days (HR 2.84) survival. The C ...
198 citations
TL;DR: PCT accurately predicts the presence of bacteremia and bacterial load in patients with febrile UTI and may be a helpful biomarker to limit use of blood culture resources.
Abstract: Guidelines recommend that two blood cultures be performed in patients with febrile urinary tract infection (UTI), to detect bacteremia and help diagnose urosepsis. The usefulness and cost-effectiveness of this practice have been criticized. This study aimed to evaluate clinical characteristics and the biomarker procalcitonin (PCT) as an aid in predicting bacteremia. A prospective observational multicenter cohort study included consecutive adults with febrile UTI in 35 primary care units and 8 emergency departments of 7 regional hospitals. Clinical and microbiological data were collected and PCT and time to positivity (TTP) of blood culture were measured. Of 581 evaluable patients, 136 (23%) had bacteremia. The median age was 66 years (interquartile range 46 to 78 years) and 219 (38%) were male. We evaluated three different models: a clinical model including seven bed-side characteristics, the clinical model plus PCT, and a PCT only model. The diagnostic abilities of these models as reflected by area under the curve of the receiver operating characteristic were 0.71 (95% confidence interval (CI): 0.66 to 0.76), 0.79 (95% CI: 0.75 to 0.83) and 0.73 (95% CI: 0.68 to 0.77) respectively. Calculating corresponding sensitivity and specificity for the presence of bacteremia after each step of adding a significant predictor in the model yielded that the PCT > 0.25 μg/l only model had the best diagnostic performance (sensitivity 0.95; 95% CI: 0.89 to 0.98, specificity 0.50; 95% CI: 0.46 to 0.55). Using PCT as a single decision tool, this would result in 40% fewer blood cultures being taken, while still identifying 94 to 99% of patients with bacteremia. The TTP of E. coli positive blood cultures was linearly correlated with the PCT log value; the higher the PCT the shorter the TTP (R2 = 0.278, P = 0.007). PCT accurately predicts the presence of bacteremia and bacterial load in patients with febrile UTI. This may be a helpful biomarker to limit use of blood culture resources.
172 citations
TL;DR: Pcalcitonin is superior to other commonly used markers in its specificity for bacterial infection, as an indicator of disease severity and risk of death, and mainly as a guide to the necessity for antibiotic therapy.
Abstract: In patients with community-acquired pneumonia, traditional criteria of infection based on clinical signs and symptoms, clinical scoring systems, and general inflammatory indicators (for example, leukocytosis, fever, C-reactive protein and blood cultures) are often of limited clinical value and remain an unreliable guide to etiology, optimal therapy and prognosis. Procalcitonin is superior to other commonly used markers in its specificity for bacterial infection (allowing alternative diagnoses to be excluded), as an indicator of disease severity and risk of death, and mainly as a guide to the necessity for antibiotic therapy. It can therefore be viewed as a diagnostic, prognostic, and perhaps even theragnostic test. It more closely matches the criteria for usefulness than other candidate biomarkers such as C-reactive protein, which is rather a nonspecific marker of acute phase inflammation, and proinflammatory cytokines such as plasma IL-6 levels that are highly variable, cumbersome to measure, and lack specificity for systemic infection. Elevated levels of pro-adrenomedullin, copeptin (which is produced in equimolar amounts to vasopressin), natriuretic peptides and cortisol are significantly related to mortality in community-acquired pneumonia, as are other prohormones such as pro-atrial natriuretic peptide, coagulation markers, and other combinations of inflammatory cytokine profiles. However, all biomarkers have weaknesses as well as strengths. None should be used on its own; and none is anything more than an aid in the exercise of clinical judgment based upon a synthesis of available clinical, physiologic and laboratory features in each patient.
165 citations
TL;DR: Procalcitonin (PCT) seems to be the most helpful laboratory marker for the differentiation of causes of fever, particularly in autoimmune, autoinflammatory and malignant diseases.
165 citations
TL;DR: A simple one-point PCT measurement for guiding decisions on antibiotic treatment is non-inferior to standard treatment in terms of safety, and effectively reduced the antibiotic treatment rate by 41.6%.
Abstract: Increasing worldwide development of antimicrobial resistance and the association of resistance development and antibiotic overuse make it necessary to seek strategies for safely reducing antibiotic use and selection pressure. In a first step, in a non-interventional study, the antibiotic prescription rates, initial procalcitonin (PCT) levels and outcome of 702 patients presenting with acute respiratory infection at 45 primary care physicians were observed. The second part was a randomised controlled non-inferiority trial comparing standard care with PCT-guided antimicrobial treatment in 550 patients in the same setting. Antibiotics were recommended at a PCT threshold of 0.25 ng·mL −1 . Clinical overruling was permitted. The primary end-point for non-inferiority was number of days with significant health impairment after 14 days. Antibiotics were prescribed in 30.3% of enrolled patients in the non-interventional study. In the interventional study, 36.7% of patients in the control group received antibiotics as compared to 21.5% in the PCT-guided group (41.6% reduction). In the modified intention-to-treat analysis, the numbers of days with significant health impairment were similar (mean 9.04 versus 9.00 for PCT-guided and control group, respectively; difference 0.04; 95% confidence interval -0.73–0.81). This was also true after adjusting for the most important confounders. In the PCT group, advice was overruled in 36 cases. There was no significant difference in primary end-point when comparing the PCT group treated as advised, the overruled PCT group and the control group (9.008 versus 9.250 versus 9.000 days; p = 0.9605). A simple one-point PCT measurement for guiding decisions on antibiotic treatment is non-inferior to standard treatment in terms of safety, and effectively reduced the antibiotic treatment rate by 41.6%.
149 citations
TL;DR: PCT concentrations were higher in more severe forms of severe sepsis, but a substantial concentration decrease was more important for survival than absolute values.
Abstract: Introduction: This prospective study investigated the predictive value of procalcitonin (PCT) for survival in 242 adult patients with severe sepsis and septic shock treated in intensive care. Methods: PCT was analyzed from blood samples of all patients at baseline, and 155 patients 72 hours later. Results: The median PCT serum concentration on day 0 was 5.0 ng/ml (interquartile range (IQR) 1.0 and 20.1 ng/ml) and 1.3 ng/ml (IQR 0.5 and 5.8 ng/ml) 72 hours later. Hospital mortality was 25.6% (62/242). Median PCT concentrations in patients with community-acquired infections were higher than with nosocomial infections (P = 0.001). Blood cultures were positive in 28.5% of patients (n = 69), and severe sepsis with positive blood cultures was associated with higher PCT levels than with negative cultures (P = 50% (by 72 hours) compared to those with a < 50% decrease (12.2% vs. 29.8%, P = 0.007). Conclusions: PCT concentrations were higher in more severe forms of severe sepsis, but a substantial concentration decrease was more important for survival than absolute values.
146 citations
TL;DR: Serial PCT determinations allow to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis and before this PCT-guided strategy can be recommended, its safety has to be confirmed in a larger cohort of neonates.
Abstract: Background: Diagnosis of neonatal early-onset sepsis is difficult because clinical signs and laboratory tests are non-specific. Early antibiotic therapy is crucial for treatment suc
141 citations
TL;DR: This review aims to provide physicians with an overview of the strengths and limitations of procalcitonin guidance for antibiotic therapy when used in different clinical settings and in patients with different underlying infections.
Abstract: Procalcitonin is a surrogate biomarker for estimating the likelihood of a bacterial infection. Procalcitonin-guided initiation and termination of antibiotic therapy is a novel approach utilized to reduce antibiotic overuse. This is essential to decrease the risk of side effects and emerging bacterial multiresistance. Interpretation of procalcitonin levels must always comprise the clinical setting and knowledge about assay characteristics. Only highly sensitive procalcitonin assays should be used in clinical practice and cut-off ranges must be adapted to the disease and setting. Highly sensitive procalcitonin measurements, embedded in diagnosis-specific clinical algorithms, have been shown to markedly reduce the overuse of antibiotic therapy without increasing risk to patients in 11 randomized controlled trials including over 3500 patients from different European countries. In primary care and emergency department patients with mild and mostly viral respiratory infections (acute bronchitis), the initial prescription of antibiotics was reduced by 30-80%. In hospitalized and more severely ill patients with community-acquired pneumonia and sepsis, the main effect was a reduction of the duration of antibiotic courses by 25-65%. This review aims to provide physicians with an overview of the strengths and limitations of procalcitonin guidance for antibiotic therapy when used in different clinical settings and in patients with different underlying infections.
TL;DR: Five biomarkers from distinct biologic pathways were strong and specific predictors for short-term adverse outcome and improved clinical risk scores in CAP and non-pneumonic LRTI.
Abstract: Measurement of prohormones representing different pathophysiological pathways could enhance risk stratification in patients with community-acquired pneumonia (CAP) and other lower respiratory tract infections (LRTI). We assessed clinical parameters and five biomarkers, the precursor levels of adrenomedullin (ADM), endothelin-1 (ET1), atrial-natriuretic peptide (ANP), anti-diuretic hormone (copeptin), and procalcitonin in patients with LRTI and CAP enrolled in the multicenter ProHOSP study. We compared the prognostic accuracy of these biomarkers with the pneumonia severity index (PSI) and CURB65 (Confusion, Urea, Respiratory rate, Blood pressure, Age 65) score to predict serious complications defined as death, ICU admission and disease-specific complications using receiver operating curves (ROC) and reclassification methods. During the 30 days of follow-up, 134 serious complications occurred in 925 (14.5%) patients with CAP. Both PSI and CURB65 overestimated the observed mortality (X2 goodness of fit test: P = 0.003 and 0.01). ProADM or proET1 alone had stronger discriminatory powers than the PSI or CURB65 score or any of either score components to predict serious complications. Adding proADM alone (or all five biomarkers jointly) to the PSI and CURB65 scores, significantly increased the area under the curve (AUC) for PSI from 0.69 to 0.75, and for CURB65 from 0.66 to 0.73 (P < 0.001, for both scores). Reclassification methods also established highly significant improvement (P < 0.001) for models with biomarkers if clinical covariates were more flexibly adjusted for. The developed prediction models with biomarkers extrapolated well if evaluated in 434 patients with non-CAP LRTIs. Five biomarkers from distinct biologic pathways were strong and specific predictors for short-term adverse outcome and improved clinical risk scores in CAP and non-pneumonic LRTI. Intervention studies are warranted to show whether an improved risk prognostication with biomarkers translates into a better clinical management and superior allocation of health care resources. NCT00350987.
TL;DR: Clinically, PCT levels may help in decisions regarding the need for empirical antibiotic therapy, “source control” of infection, and duration of antibiotic therapy.
Abstract: Procalcitonin (PCT) is synthesized by a large number of tissues and organs in response to invasion by pathogenic bacteria, fungi, and some parasites. Current PCT assays are rapid, specific, and of sufficient sensitivity to detect increases in PCT serum levels within 4 to 6 h of initiation of infection. Clinically, PCT levels may help in decisions regarding the need for empirical antibiotic therapy, “source control” of infection, and duration of antibiotic therapy. The addition of PCT levels to bacterial culture and viral detection results can assist with the separation of colonization and invasion by pathogenic bacteria.
TL;DR: Contrary to the current literature, this study suggests that patients with low PCT values do benefit from antibiotics, and CRP might be a more valuable marker in these patients.
TL;DR: Prevalence of upper-respiratory viral infection, as detected from nasopharyngeal swab by RT-PCR, is high in AECOPD and low after clinical recovery, suggesting that A ECOPD frequently are triggered by viral infections initiated in the upper- Respiratory tract.
TL;DR: The current knowledge of PCT and its use in the clinical laboratory setting is reviewed and it is shown that PCT is a biomarker that exhibits greater specificity than other proinflammatory markers in identifying patients with sepsis and can be used in the diagnosis of bacterial infections.
Abstract: Sepsis is the systemic response to infection by microbial organisms. A differential diagnosis of infection caused by either bacteria or other microbial organisms is essential for effective treatment and prognostic assessment. Current clinical laboratory methods in the diagnosis of bacterial infections are either non-specific or require longer turnaround times. Procalcitonin (PCT) is a biomarker that exhibits greater specificity than other proinflammatory markers (eg, cytokines) in identifying patients with sepsis and can be used in the diagnosis of bacterial infections. In this article, we review the current knowledge of PCT and its use in the clinical laboratory setting.
TL;DR: Eosinopenia is a very sensitive yet not specific serological marker of sepsis in the intensive care unit and can be utilized to guide physicians in the diagnosis of septicaemia.
TL;DR: The thromboelastometry lysis index proved to be a more reliable biomarker of severe sepsis in critically ill adults than were procalcitonin, interleukin 6, and C-reactive protein, and the results demonstrate that early involvement of the hemostatic system is a common event in severe Sepsis.
Abstract: Established biomarkers for the diagnosis of sepsis are procalcitonin, interleukin 6, and C-reactive protein. Although sepsis evokes changes of coagulation and fibrinolysis, it is unknown whether thromboelastometry can detect these alterations. We investigated whether thromboelastometry variables are suitable as biomarkers for severe sepsis in critically ill adults. In the observational cohort study, blood samples were obtained from patients on the day of diagnosis of severe sepsis (n = 56) and from postoperative patients (n = 52), and clotting time, clot formation time, maximum clot firmness, alpha angle, and lysis index were measured with thromboelastometry. In addition, procalcitonin, interleukin 6, and C-reactive protein levels were determined. For comparison of biomarkers, receiver operating characteristic (ROC) curves were used, and the optimal cut-offs and odds ratios were calculated. In comparison with postoperative controls, patients with sepsis showed an increase in lysis index (97% ± 0.3 versus 92 ± 0.5; P 96.5%, resulting in a sensitivity of 84.2%, and a specificity of 94.2%, with an odds ratio of 85.3 (CI 21.7 - 334.5). The thromboelastometry lysis index proved to be a more reliable biomarker of severe sepsis in critically ill adults than were procalcitonin, interleukin 6, and C-reactive protein. The results also demonstrate that early involvement of the hemostatic system is a common event in severe sepsis.
TL;DR: The results of the first study suggest that there is a low risk on discontinuing antibiotic treatment too early, resulting in the development of a neonatal infection with its morbidity and mortality.
Abstract: Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life threatening complications. Diagnosis of neonatal sepsis is difficult because of the variable and nonspecific clinical presentation. Therefore, many newborns with nonspecific symptoms are started on antibiotic treatment before the presence of sepsis has been proven. With our recently published single-centre intervention study we were able to show that Procalcitonin determinations allowed to shorten the duration of antibiotic therapy in newborns with suspected early-onset sepsis. The study is designed as randomized controlled international multicenter intervention trial on the efficacy and safety of Procalcitonin guided treatment. Term and near-term infants (gestational age ≥ 34 0/7 weeks) with suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy will be included. The duration of antibiotic therapy in the standard group is based on the attending physician's assessment of the likelihood of infection (infection unlikely, possible, probable or proven). In the Procalcitonin group, if infection is considered to be unlikely or possible, antibiotic therapy is discontinued when two consecutive Procalcitonin values are within the normal range. Co-primary outcome measures are the duration of antibiotic therapy (superiority aspect of the trial) and the proportion of infants with a recurrence of infection requiring additional courses of antibiotic therapy and/or death in the first month of life (safety of study intervention, non-inferiority aspect of the trial). The number of infants to be included equals 800 per arm. With these numbers the power of the study to demonstrate superiority for duration of antibiotic therapy as well as non-inferiority regarding safety, i.e. excluding a disadvantage difference larger than 2% for the experimental arm, will both be greater than 80%. Benefit of the study is a possible limitation of unnecessary use of antibiotics. The results of our first study suggest that there is a low risk on discontinuing antibiotic treatment too early, resulting in the development of a neonatal infection with its morbidity and mortality. This trial is registered in the U.S. National Institutes of Health's register, located at http://www.clinicaltrials.gov
. (NCT00854932).
TL;DR: Serum procalcitonin is a helpful diagnostic marker supporting clinical and microbiological findings for more reliable differentiation of infectious from noninfectious causes of fever after orthopaedic surgery.
Abstract: BACKGROUND: Early diagnosis of postoperative orthopaedic infections is important in order to rapidly initiate adequate antimicrobial therapy. There are currently no reliable diagnostic markers to differentiate infectious from noninfectious causes of postoperative fever. We investigated the value of the serum procalcitonin level in febrile patients after orthopaedic surgery. METHODS: We prospectively evaluated 103 consecutive patients with new onset of fever within ten days after orthopaedic surgery. Fever episodes were classified by two independent investigators who were blinded to procalcitonin results as infectious or noninfectious origin. White blood-cell count, C-reactive protein level, and procalcitonin level were assessed on days 0, 1, and 3 of the postoperative fever. RESULTS: Infection was diagnosed in forty-five (44%) of 103 patients and involved the respiratory tract (eighteen patients), urinary tract (eighteen), joints (four), surgical site (two), bloodstream (two), and soft tissues (one). Unlike C-reactive protein levels and white blood-cell counts, procalcitonin values were significantly higher in patients with infection compared with patients without infection on the day of fever onset (p = 0.04), day 1 (p = 0.07), and day 3 (p = 0.003). Receiver-operating characteristics demonstrated that procalcitonin had the highest diagnostic accuracy, with a value of 0.62, 0.62, and 0.71 on days 0, 1, and 3, respectively. In a multivariate logistic regression analysis, procalcitonin was a significant predictor for postoperative infection on days 0, 1, and 3 of fever with an odds ratio of 2.3 (95% confidence interval, 1.1 to 4.4), 2.3 (95% confidence interval, 1.1 to 5.2), and 3.3 (95% confidence interval, 1.2 to 9.0), respectively. CONCLUSIONS: Serum procalcitonin is a helpful diagnostic marker supporting clinical and microbiological findings for more reliable differentiation of infectious from noninfectious causes of fever after orthopaedic surgery.
TL;DR: Procalcitonin measurement potentially assists in the discrimination between severe lower respiratory tract infections of bacterial and 2009 H1N1 origin, although less effectively than CRP.
Abstract: To examine whether, in an adult intensive care unit (ICU), procalcitonin or C-reactive protein (CRP) levels discriminated between 2009 H1N1 influenza infection and community-acquired pneumonia of bacterial origin. A retrospective observational study performed at an Australian hospital over a 4-month winter period during the 2009 H1N1 influenza pandemic. Levels on admission of procalcitonin and CRP were compared between patients admitted to the ICU with community-acquired pneumonia of bacterial and 2009 H1N1 origin. Compared to those with bacterial or mixed infection (n = 9), patients with 2009 H1N1 infection (n = 16) were significantly more likely to have bilateral chest X-ray infiltrates, lower APACHE scores, more prolonged lengths of stay in ICU and lower white cell count, procalcitonin and CRP levels. Using a cutoff of >0.8 ng/ml, the sensitivity and specificity of procalcitonin for detection of patients with bacterial/mixed infection were 100 and 62%, respectively. A CRP cutoff of >200 mg/l best identified patients with bacterial/mixed infection (sensitivity 100%, specificity 87.5%). In combination, procalcitonin levels >0.8 ng/ml and CRP >200 mg/l had optimal sensitivity (100%), specificity (94%), negative predictive value (100%) and positive predictive value (90%). Receiver-operating characteristic curve analysis suggested the diagnostic accuracy of procalcitonin may be inferior to CRP in this setting. Procalcitonin measurement potentially assists in the discrimination between severe lower respiratory tract infections of bacterial and 2009 H1N1 origin, although less effectively than CRP. Low values, particularly when combined with low CRP levels, suggested bacterial infection, alone or in combination with influenza, was unlikely.
TL;DR: Results of earlier studies showing that circulating Gas6 is increased in sepsis and related syndromes are confirmed and the concentrations of Gas6 and sAxl correlate with a number of inflammatory markers, suggesting a role in systemic inflammation.
Abstract: Introduction: Gas6, the protein product of the growth arrest specific gene 6, is present in human circulation at subnanomolar concentrations. It is secreted by endothelial cells and is important for the activation of endothelium during inflammation. Axl, the tyrosine kinase receptor for Gas6, is also present in endothelium and can be cleaved and released into the circulation. The soluble of form Axl (sAxl), which is present in plasma, can bind Gas6 and inhibit Axl-mediated cell signalling. Methods: We have developed reproducible and accurate enzyme-linked immunosorbent assays for both Gas6 and sAxl and used them to investigate plasma samples from 70 patients with severe sepsis, 99 patients with sepsis, 42 patients with various infections causing fever but no systemic inflammatory response syndrome (SIRS), 20 patients with SIRS without verified infection, and 100 blood donors that served as controls. Correlations between Gas6 and sAxl concentrations and other commonly used analytes were investigated. Results: The patients with severe sepsis, sepsis, infection or SIRS had all increased concentrations of Gas6, approximately double compared to what was found in the controls. The concentrations of sAxl were also increased in the patient groups compared to the controls. Gas6 correlated with C-reactive protein, procalcitonin and interleukin 6, whereas sAxl correlated to bilirubin and procalcitonin. Conclusions: We can confirm results of earlier studies showing that circulating Gas6 is increased in sepsis and related syndromes. sAxl is increased, but less pronounced than Gas6. The concentrations of Gas6 and sAxl correlate with a number of inflammatory markers, suggesting a role in systemic inflammation.
TL;DR: It is suggested that PCT may be a valuable addition to currently used markers of infection for diagnosis of infection and prognosis in patients with fever at the Emergency Department.
Abstract: Objective: First, to determine whether procalcitonin (PCT) significanty adds diagnostic value in terms of sensitivity and specificity to a common set of markers of infection, including C-reactive protein (CRP), at the Emergency Department. Second, to create a simple scoring rule implementing PCT values. Third, to determine and compare associations of CRP and PCT with clinical outcomes. Design: The additional diagnostic value of PCT was determined using multiple logistic regression analysis. A score was developed to help distinguish patients with a culture-proven bacterial infection from patients not needing antibiotic treatment using 16 potential clinical and laboratory variables. The prognostic value of CRP and PCT was determined using Spearman's correlation and logistic regression. Setting: Emergency Department of a 310-bed teaching hospital. Patients: Patients between 18 and 85 years old presenting with fever to the Emergency Department. Interventions: None. Measurements and Main Results: A total of 211 patients were studied (infection confirmed, n = 73; infection likely, n = 58; infection not excluded, n = 46; no infection, n = 34). CRP and chills were the strongest predictors for the diagnosis of bacterial infection. After addition of PCT to these parameters, model fit significantly improved (p = .003). The resulting scoring rule (score = 0.01 * CRP + 2 * chills + 1 * PCT) was characterized by an AUC value of 0.83 (sensitivity 79%; specificity of 71%), which was more accurate than physician judgment or SIRS (systemic inflammatory response syndrome). PCT levels were significantly associated with admission to a special care unit, duration of intravenous antibiotic use, total duration of antibiotic treatment, and length of hospital stay, whereas CRP was related only to the latter two variables. Conclusions: These data suggest that PCT may be a valuable addition to currently used markers of infection for diagnosis of infection and prognosis in patients with fever at the Emergency Department. (Crit Care Med 2010; 38:457-463)
TL;DR: Neither PCT and CRP threshold values nor their kinetics can predict VAP survival or septic shock development.
Abstract: We evaluated the performance of procalcitonin (PCT) and C-reactive protein (CRP) threshold values and kinetics as predictors of ventilator-associated pneumonia (VAP) survival and septic shock development.
45 adult patients with VAP were studied. Serum CRP and PCT levels and the Sequential Organ Failure Assessment (SOFA) score were measured on days 1, 4 and 7 (D1, D4, D7) of VAP and their variations between different days (kinetics) were calculated (ΔPCT, ΔCRP). A multivariate logistic regression model was constructed with either VAP 28-day survival or septic shock development as dependent variables, and PCT values, CRP values, kinetics, age, sex, SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) II score as independent variables.
No difference was found in CRP levels between survivors and nonsurvivors. Nonsurvivors had significantly higher PCT levels on D1 and D7. In the multivariate analysis, the only factors predicting VAP survival were ΔPCT7-1 (OR 7.23, 95% CI 0.008–0.468) and ΔCRP7-4 (OR 4.59, 95% CI 0.013–0.824). VAP patients who developed septic shock had significantly higher CRP levels on D1 and D7 and higher PCT levels on D1 and D4. The only factor predicting the development of septic shock was SOFA on D1 (OR 7.44, 95% CI 1.330–5.715).
Neither PCT and CRP threshold values nor their kinetics can predict VAP survival or septic shock development.
TL;DR: The PCT test showed moderate accuracy in diagnosing neonatal sepsis, regardless of differences in diagnostic criteria and time points for testing, and for the diagnosis of LONS, the PCTtest showed better accuracy than the CRP test.
Abstract: A meta-analysis was performed to assess the accuracy of the procalcitonin (PCT) test for diagnosing neonatal sepsis. The major databases, MEDLINE, EMBASE and the Cochrane Library were searched for studies published between January 1996 and May 2009 that evaluated PCT as a diagnostic marker for neonatal sepsis and provided sufficient data to calculate sensitivity and specificity. Twenty-two studies were included in the analysis. Trials that evaluated the PCT test for the diagnosis of early-onset neonatal sepsis at different time points (birth, 0-12 h, 12-24 h, and 24-48 h) and late-onset neonatal sepsis (LONS) all showed moderate accuracy (Q* = 0.79, 0.86, 0.81, 0.82, and 0.77, respectively). The PCT test was more accurate than the C-reactive protein (CRP) test for the diagnosis of LONS. A sensitivity analysis found that differences in PCT assay producer, gestational age and severity of sepsis in the study population may partially explain the between-studies heterogeneity. The PCT test showed moderate accuracy in diagnosing neonatal sepsis, regardless of differences in diagnostic criteria and time points for testing. For the diagnosis of LONS, the PCT test showed better accuracy than the CRP test. PCT is a valuable additional tool for the diagnosis of neonatal sepsis.
TL;DR: To evaluate the diagnostic performance of procalcitonin (PCT) in elderly patients with bacterial infection in the emergency department (ED), a large number of them are elderly and have a history of infection.
Abstract: OBJECTIVES: To evaluate the diagnostic performance of procalcitonin (PCT) in elderly patients with bacterial infection in the emergency department (ED).
DESIGN: Prospective.
SETTING: ED of a tertiary care hospital.
PARTICIPANTS: Elderly patients with systemic inflammatory response syndrome (SIRS) enrolled from September 2004 through August 2005.
MEASUREMENTS: A serum sample for the measurement of PCT, two sets of blood cultures, and other cultures of relevant specimens from infection sites were collected in the ED. Two independent experts blinded to the PCT results classified the patients into bacterial infection and nonbacterial infection groups.
RESULTS: Of the 262 patients with SIRS enrolled, 204 were classified as having bacterial infection and 48 as having bacteremia. PCT levels were significantly higher in patients with bacteremia than in those without. The area under the receiver operating characteristic curve for identification of bacteremia according to PCT was 0.817 for the old-old group (≥75), significantly higher than 0.639 for the young-old group (65–74); P=.02). The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of PCT for bacteremia in patients aged 75 and older were 96.0%, 68.3%, 33.8%, and 98.8%, respectively, with a PCT cutoff value of 0.38 ng/mL.
CONCLUSION: PCT is sensitive for diagnosing bacteremia in elderly patients with SIRS at ED admission but is helpful in excluding bacteremia only in those aged 75 and older. PCT is not an independent predictor of local infections in these patients.
TL;DR: Normal concentrations of CF-DNA can exclude the presence of an infection in febrile patients, and very high concentrations stratify the severity of infections, showing a high prognostic value to predict mortality in the absence of other causes for elevated CF- DNA.
Abstract: BackgroundCirculating 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.MethodsConcentrations 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.ResultsConcentrations 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 surviv...
TL;DR: In this paper, the authors investigated the time course of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) levels in patients with therapeutic hypothermia after cardiac arrest.
Abstract: Eur J Clin Invest 2010; 40 (4): 376–381
Abstract
Introduction The aim of this study was to investigate time course of procalcitonin (PCT), C-reactive protein (CRP) and white blood cell (WBC) levels in patients with therapeutic hypothermia after cardiac arrest.
Methods We retrospectively assessed laboratory and clinical data in a consecutive cohort of patients admitted to the medical intensive-care-unit of the University Hospital in Basel, Switzerland, in whom therapeutic hypothermia was induced because of cardiac arrest between December 2007 and January 2009. Infection was considered based on microbiological evidence (restricted definition) and/or clinical evidence of infection with prescription of antibiotics (extended definition).
Results From 34 included patients, 25 had respiratory tract infection based on the clinical judgment and in 18 microbiological cultures turned positive (restricted definition). PCT concentrations were highest on the first day after hypothermia and showed a steady decrease until day 7 without differences in patients with and without presumed infection. CRP concentrations increased to a peak level at days 3–4 followed by a steady decrease; CRP concentrations were higher in patients with clinical diagnosis of infection on day 4 (P = 0·02); and in patients with evidence of bacterial growth in cultures on days 4 and 5 (P = 0·01 and P = 0·006). WBC remained unchanged after hypothermia without differences between patients with and without infection.
Conclusion High initial values of PCT and high peak levels after 3–4 days of CRP were found in patients with induction of hypothermia after cardiac arrest. This increase was unspecific and mirrors rather an inflammatory reaction than true underlying infection, limiting the diagnostic potential for early antibiotic stewardship in these patients.
TL;DR: The data indicate that a low PCT value in a critically ill septic patient is more likely to be related to candidemia than to bacteremia, and this role in fungal infections is less defined than in patients with candidemia.
TL;DR: This study showed that alveolar procalcitonin performed by BAL does not help the clinician to identify VAP and confirmed that serum procalCitonin is not an accurate marker of VAP.
Abstract: Early and adequate treatment of ventilator-associated pneumonia (VAP) is mandatory to improve the outcome. The aim of this study was to evaluate, in medical ICU patients, the respective and combined impact of the Clinical Pulmonary Infection Score (CPIS), broncho-alveolar lavage (BAL) gram staining, endotracheal aspirate and a biomarker (procalcitonin) for the early diagnosis of VAP. Prospective, observational study A medical intensive care unit in a teaching hospital. Over an 8-month period, we prospectively included 57 patients suspected of having 86 episodes of VAP. The day of suspicion, a BAL as well as alveolar and serum procalcitonin determinations and evaluation of CPIS were performed. Of 86 BAL performed, 48 were considered positive (cutoff of 104 cfu ml−1). We found no differences in alveolar or serum procalcitonin between VAP and non-VAP patients. Including procalcitonin in the CPIS score did not increase its accuracy (55%) for the diagnosis of VAP. The best tests to predict VAP were modified CPIS (threshold at 6) combined with microbiological data. Indeed, both routinely twice weekly performed endotracheal aspiration at a threshold of 105 cfu ml−1 and BAL gram staining improved pre-test diagnostic accuracy of VAP (77 and 66%, respectively). This study showed that alveolar procalcitonin performed by BAL does not help the clinician to identify VAP. It confirmed that serum procalcitonin is not an accurate marker of VAP. In contrast, microbiological resources available at the time of VAP suspicion (BAL gram staining, last available endotracheal aspirate) combined or not with CPIS are helpful in distinguishing VAP diagnosed by BAL from patients with a negative BAL.