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Showing papers on "Procalcitonin published in 2012"


Journal ArticleDOI
TL;DR: An update on the current evidence on the use of CRP in neonates is given and some topics are still not fully understood, such as the influence of noninfectious factors on CRP levels in healthy as well as in symptomatic neonates and the role of gestational age and birthweight onCRP kinetics.
Abstract: C-reactive protein (CRP) is one of the most studied and most used laboratory tests for neonatal sepsis. As part of the acute-phase reaction to infection, it plays a central role in the humoral response to bacterial invasion. The delayed synthesis during the inflammatory response accounts for its low sensitivity during the early phases of the disease. Diagnostic accuracy clearly improves by the performance of serial determinations and by the combination with earlier markers such as interleukins or procalcitonin. CRP is as well particularly useful for monitoring the response to treatment and guiding antibiotic therapy, though nothing replaces the clinical impression and the gold standard (i.e. culture results). In spite of the large amount of research done on CRP in neonates, some topics are still not fully understood, such as the influence of noninfectious factors on CRP levels in healthy as well as in symptomatic neonates and the role of gestational age and birthweight on CRP kinetics. In this review, we aim to give an update on the current evidence on the use of CRP in neonates.

327 citations


Journal ArticleDOI
TL;DR: This prospective study demonstrates the high performance of a bioscore combining the PMN CD64 index together with PCT and sTREM-1 serum levels in diagnosing sepsis in the critically ill patient.
Abstract: Rationale: Although the outcome of sepsis benefits from the prompt administration of appropriate antibiotics on correct diagnosis, the assessmentofinfectionincriticallyillpatientsisoftenachallengefor clinicians. Inthissetting,simple biomarkers, especiallywhenusedin combination, could prove useful. Objectives: To determine the usefulness of combination biomarkers to diagnose sepsis. Methods: Three hundred consecutive patients were enrolled to construct a biologic score that was next validated in an independent prospective cohort of 79 critically ill patients from another center. MeasurementandMainResults:Plasmaconcentrationsofsolubletriggering receptor expressed on myeloid cells-1 (sTREM-1) and procalcitonin (PCT) were assayed, and the expression of the high-affinity immunoglobulin-Fc fragment receptor I (FcgRI) CD64 on neutrophils (polymorphonuclear [PMN] CD64 index) in flow cytometry was measured. A “bioscore” combining these biomarkers was constructed. Serum concentrations of PCT and sTREM-1 and the PMN CD64 index were higher in patients with sepsis compared with all others (P , 0.001 for the three markers). These biomarkers were all independent predictors of infection, the best receiver-operating characteristic curve being obtained for the PMN CD64 index. The performance of the bioscore, better than that of each individual biomarker, was externally confirmed in the validation cohort. Conclusions: This prospective study, including inceptive and valida

256 citations


Journal ArticleDOI
TL;DR: Presepsin is useful for the diagnosis of sepsis, and it is superior to conventional markers and blood culture.

243 citations


Journal ArticleDOI
TL;DR: This individual patient data meta-analysis of clinical trials investigating procalcitonin algorithms for antibiotic decision making found no increased risk of death or setting-specific treatment failure but did find significantly lower antibiotic exposure across different acute respiratory infections and clinical settings.
Abstract: Acute respiratory infections (ARIs) comprise a large and heterogeneous group of infections, including bacterial infections, viral infections, and infections of other etiologies. Early initiation of adequate antibiotic therapy is the cornerstone in the treatment of bacterial ARIs and is associated with improved clinical outcomes [1, 2]. However, overuse of antibiotics by overprescription in outpatients with bronchitis [3], for instance, and prolonged duration of antibiotic therapy in patients with bacterial ARIs in the hospital and intensive care setting is associated with increased resistance for common bacteria, high costs, and adverse drug reactions [4, 5]. The safe reduction in antibiotic use is therefore of utmost importance. In recent years, procalcitonin (PCT) has emerged as a promising marker for the diagnosis of bacterial infections because higher levels are found in severe bacterial infections than in viral infections and nonspecific inflammatory diseases [6, 7]. Hence, PCT may be used to support clinical decision making for the initiation and discontinuation of antibiotic therapy [8]. Randomized controlled trials (RCTs) have demonstrated the feasibility of such a strategy in different ARI patient populations and different settings ranging from primary care [9, 10] to emergency departments (EDs), hospital wards [11–17], and intensive care units (ICUs) [18–22]. Most individual trials, however, lacked the statistical power to assess the risk for mortality and severe infectious disease complications associated with PCT-guided decision making. We undertook an individual patient data meta-analysis of trials comparing the effects of using PCT to guide initiation and duration of antibiotic treatment in patients with ARI assigned to routine PCT measurement or standard of care without PCT measurement. The aim of this analysis was to assess the safety and efficacy of this approach over a large range of patients with varying severity of ARIs.

237 citations


Journal ArticleDOI
TL;DR: This study validates previous results from controlled trials in real-life conditions and demonstrates that following a PCT algorithm effectively reduces antibiotic use without increasing the risk of complications.
Abstract: Background In controlled studies, procalcitonin (PCT) has safely and effectively reduced antibiotic drug use for lower respiratory tract infections (LRTIs). However, controlled trial data may not reflect real life. Methods We performed an observational quality surveillance in 14 centers in Switzerland, France, and the United States. Consecutive adults with LRTI presenting to emergency departments or outpatient offices were enrolled and registered on a website, which provided a previously published PCT algorithm for antibiotic guidance. The primary end point was duration of antibiotic therapy within 30 days. Results Of 1759 patients, 86.4% had a final diagnosis of LRTI (community-acquired pneumonia, 53.7%; acute exacerbation of chronic obstructive pulmonary disease, 17.1%; and bronchitis, 14.4%). Algorithm compliance overall was 68.2%, with differences between diagnoses (bronchitis, 81.0%; AECOPD, 70.1%; and community-acquired pneumonia, 63.7%; P Conclusions This study validates previous results from controlled trials in real-life conditions and demonstrates that following a PCT algorithm effectively reduces antibiotic use without increasing the risk of complications. Preexisting differences in antibiotic prescribing affect compliance with antibiotic stewardship efforts. Trial Registration isrctn.org Identifier: ISRCTN40854211

144 citations


Journal ArticleDOI
15 Jun 2012-PLOS ONE
TL;DR: Logistic regression analysis showed that sepsis stage, Sequential Organ Failure Assessment scores, Acute Physiology and Chronic Health Evaluation II scores, and miR-15a,miR-16, mi-193b*, andMiR-483-5p were associated with death from sepsi.
Abstract: Background: Sepsis is the leading cause of death in Intensive Care Unit. Novel biomarkers and targets of treatment were still needed to improve the mortality. Our goal of the prospective study was to investigate if serum miRNAs identified in genome-wide scans could predict sepsis mortality. Methodology/Principal findings: 214 sepsis patients participated in the study. Solexa sequencing followed by qRT-PCR were used to test for differences in the levels of miRNAs between survivors and non-survivors of sepsis patients. miR-223, miR-15a, miR-16, miR-122, miR-193* and miR-483-5p were significantly differentially expressed, and the area under curve of the six miRNAs predictive mortality value ranged from 0.610 (95%CI, 0.523-0.697) to 0.790 (95%CI, 0.719-0.861). Logistic regression analysis showed that sepsis stage, APACHE II score, miR-15a, miR-16, miR-193b* and miR-483-5p were correlated to the death of sepsis and area under curve of the six variables predictive value was 0.950 (95% Confident interval, 0.919-0.982), which was much higher than APACHE II score, SOFA score, and procalcitonin with area under curve of 0.782 (95% CI, 0.712-0.851), 0.752 (95% CI, 0.672-0.832) and 0.689 (95% CI, 0.611-0.784), respectively. When the cut off point set at 0.526, the predictive value of the six variables provided a 85.2% sensitivity and a 90.4% specificity. In addition, miR-193b* had highest odds ratio of 9.23(95% CI, 1.20-71.16). Conclusion/Significance: Six miRNAs expression profiles could be used to predict septic mortality. The predictive value was better than the indictors that used in clinical.

139 citations


Journal ArticleDOI
TL;DR: Procalcitonin performs better than leukocyte count and C-reactive protein for detecting serious bacterial infection among children with fever without source and considering the poor pooled positive likelihood ratio and acceptable pooled negative likelihood ratio, procalcionin is better for ruling out seriousacterial infection than for ruling it in.

139 citations


Journal ArticleDOI
TL;DR: A descriptive overview of the clinical value of suPAR in the diagnosis, prognosis and therapeutic guidance of sepsis is provided.
Abstract: Sepsis is the clinical syndrome derived from the host response to an infection and severe sepsis is the leading cause of death in critically ill patients. Several biomarkers have been tested for use in diagnosis and prognostication in patients with sepsis. Soluble urokinase-type plasminogen activator receptor (suPAR) levels are increased in various infectious diseases, in the blood and also in other tissues. However, the diagnostic value of suPAR in sepsis has not been well defined, especially compared to other more established biomarkers, such as C-reactive protein (CRP) and procalcitonin (PCT). On the other hand, suPAR levels have been shown to predict outcome in various kinds of bacteremia and recent data suggest they may have predictive value, similar to that of severity scores, in critically ill patients. This narrative review provides a descriptive overview of the clinical value of this biomarker in the diagnosis, prognosis and therapeutic guidance of sepsis.

138 citations


Journal ArticleDOI
TL;DR: In adult emergency department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but are inadequately discriminating to be used independently as diagnostic tools.
Abstract: Background Circulating biomarkers can facilitate sepsis diagnosis, enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers. Study Objectives To define the discriminative value of PCT, interleukin-6 (IL-6), and C-reactive protein (CRP) for suspected sepsis. Methods PCT, CRP, and IL-6 were correlated with infection likelihood, sepsis severity, and septicemia. Multivariable models were constructed for length-of-stay and discharge to a higher level of care. Results Of 336 enrolled subjects, 60% had definite infection, 13% possible infection, and 27% no infection. Of those with infection, 202 presented with sepsis, 28 with severe sepsis, and 17 with septic shock. Overall, 21% of subjects were septicemic. PCT, IL6, and CRP levels were higher in septicemia (median PCT 2.3 vs. 0.2 ng/mL; IL-6 178 vs. 72 pg/mL; CRP 106 vs. 62 mg/dL; p < 0.001). Biomarker concentrations increased with likelihood of infection and sepsis severity. Using receiver operating characteristic analysis, PCT best predicted septicemia (0.78 vs. IL-6 0.70 and CRP 0.67), but CRP better identified clinical infection (0.75 vs. PCT 0.71 and IL-6 0.69). A PCT cutoff of 0.5 ng/mL had 72.6% sensitivity and 69.5% specificity for bacteremia, as well as 40.7% sensitivity and 87.2% specificity for diagnosing infection. A combined clinical-biomarker model revealed that CRP was marginally associated with length of stay (p = 0.015), but no biomarker independently predicted discharge to a higher level of care. Conclusions In adult emergency department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but are inadequately discriminating to be used independently as diagnostic tools.

137 citations


Journal ArticleDOI
TL;DR: This work investigated the utility of concentrations of the biomarker procalcitonin alone and with clinical variables for the diagnosis of pneumonia in patients presenting to emergency departments (EDs) with a chief complaint of shortness of breath.
Abstract: Aims Biomarkers have proven their ability in the evaluation of cardiopulmonary diseases. We investigated the utility of concentrations of the biomarker procalcitonin (PCT) alone and with clinical variables for the diagnosis of pneumonia in patients presenting to emergency departments (EDs) with a chief complaint of shortness of breath. Methods and results The BACH trial was a prospective, international, study of 1641 patients presenting to EDs with dyspnoea. Blood samples were analysed for PCT and other biomarkers. Relevant clinical data were also captured. Patient outcomes were assessed at 90 days. The diagnosis of pneumonia was made using strictly validated guidelines. A model using PCT was more accurate [area under the curve (AUC) 72.3%] than any other individual clinical variable for the diagnosis of pneumonia in all patients, in those with obstructive lung disease, and in those with acute heart failure (AHF). Combining physician estimates of the probability of pneumonia with PCT values increased the accuracy to >86% for the diagnosis of pneumonia in all patients. Patients with a diagnosis of AHF and an elevated PCT concentration (>0.21 ng/mL) had a worse outcome if not treated with antibiotics (P = 0.046), while patients with low PCT values (<0.05 ng/mL) had a better outcome if they did not receive antibiotic therapy (P = 0.049). Conclusion Procalcitonin may aid in the diagnosis of pneumonia, particularly in cases with high diagnostic uncertainty. Importantly, PCT may aid in the decision to administer antibiotic therapy to patients presenting with AHF in which clinical uncertainty exists regarding a superimposed bacterial infection. Trial registration: NCT00537628

130 citations


Journal ArticleDOI
TL;DR: PCT provides important information in early stages of sepsis as well as during antimicrobial treatment, and can be useful for antimicrobial stewardship and its utilization may safely lead to significant reduction of unnecessary antimicrobial therapy.

Journal ArticleDOI
TL;DR: Procalcitonin is neither earlier nor more accurate than CRP for the detection of anastomotic leakage after elective colorectal surgery.

Journal ArticleDOI
TL;DR: Among well-appearing young infants with FWS, PCT performs better than CRP in identifying patients with invasive bacterial infections and seems to be the best marker for ruling out IBIs.
Abstract: BACKGROUND AND OBJECTIVE: 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 METHODS: Well-appearing infants aged RESULTS: 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 CONCLUSIONS: 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.

Journal ArticleDOI
TL;DR: Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aiming at decreasing the antibiotic consumption in intensive care unit patients.
Abstract: Objectives:To test the usefulness of procalcitonin serum level for the reduction of antibiotic consumption in intensive care unit patientsDesign:Single-center, prospective, randomized controlled studySetting:Five intensive care units from a tertiary teaching hospitalPatients:All consecutive adult

Journal ArticleDOI
TL;DR: Serum sTREM-1, PCT, and CRP levels each have a role in the early diagnosis of sepsis and the highest sensitivity and specificity of all indicators studied, is especially notable.
Abstract: 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

Journal ArticleDOI
TL;DR: Free hemoglobin, as determined by all 4 methods, was the best and an independent predictor for death in severe sepsis (p = 0.022 to p < 0.001), and is an important new predictor of survival in severe Sepsis.
Abstract: Introduction Hemolysis can be induced in sepsis via various mechanisms, its pathophysiological importance has been demonstrated in experimental sepsis. However, no data on free hemoglobin concentrations in human sepsis are available. In the present study we measured free hemoglobin in patients with severe sepsis as well as in postoperative patients using four methods. It was our aim to determine the potential value of free hemoglobin as a biomarker for diagnosis and outcome of severe sepsis in critical illness.


Journal ArticleDOI
TL;DR: The results showed that miR-15a had the highest area under the curve of 0.858 [95% confidence interval (CI) 0.800-0.916] for the diagnosis of sepsis compared with C reactive protein and procalcitonin this article.
Abstract: BACKGROUND Serum microRNAs may be useful biomarkers for diagnosing human diseases. We investigated serum levels of miR-15a and miR-16 in patients with sepsis and systemic inflammatory response syndrome (SIRS) without infection. METHODS We enrolled 166 sepsis patients, 32 SIRS patients, and 24 normal controls. Serum miR-15a and miR-16 expression levels were determined by quantitative reverse transcriptase polymerase chain reaction assays (qRT-PCR). RESULTS Serum miR-15a (p<0.001) and miR-16 (p<0.05) were both significantly higher in sepsis patients compared with normal controls, and miR-15a (p<0.001) and miR-16 (p<0.01) levels in SIRS patients were also significantly higher than those in normal controls. Serum miR-15a and miR-16 levels were not correlated with white blood cell counts. Receiver operating characteristic curves showed that miR-15a had the highest area under the curve of 0.858 [95% confidence interval (CI) 0.800-0.916] for the diagnosis of sepsis compared with C reactive protein and procalcitonin with areas under the curve of 0.572 (95% CI 0.479-0.665; p=0.198) and 0.605 (95% CI 0.443-0.767; p=0.168), respectively. When its cut-off point was set at 0.21, serum miR-15a had a sensitivity of 68.3% and a specificity of 94.4%. CONCLUSIONS Serum miR-15a and miR-16 can both distinguish sepsis/SIRS from normal controls. miR-15a may be a biomarker that distinguishes between sepsis and SIRS.

Journal ArticleDOI
TL;DR: Four serum miRNAs were identified as novel biomarkers of sepsis, and only miR-499-5p and Sequential Organ Failure Assessment scores had good diagnostic values to distinguish between mildSepsis and severe sepsi and septic shock.
Abstract: BACKGROUND Serum microRNAs (miRNAs) can be used as biomarkers for many kinds of diseases, and some are even better than current indicators. The aim of this study was to investigate a diagnostic role for serum miRNAs in sepsis patients. METHODS We recruited 166 patients with sepsis and 24 normal controls. Blood samples for these patients were obtained upon their admission in intensive care units of the Chinese PLA General Hospital. The expression levels of miR-223, miR-15b, miR-483-5p, miR-499-5p, miR-122, and miR-193b* were determined by quantitative reverse transcriptase polymerase chain reaction assays. RESULTS Expression levels of miR-223 were significantly higher in patients with mild sepsis (p < 0.001) and patients with severe sepsis and septic shock (p < 0.001) than in normal controls, and levels of miR-499-5p, miR-122, and miR-193b* were significantly lower than in normal controls. In addition, only miR-223 (p = 0.035) and miR-499-5p (p < 0.001) were significantly different between patients with mild sepsis and patients with severe sepsis and septic shock. miR-499-5p had the highest area under a receiver operating characteristic curve of 0.686 (95% confidence interval, 0.592-0.779). In addition, Sequential Organ Failure Assessment scores (p < 0.001), Acute Physiology and Chronic Health Evaluation II scores (p < 0.001), and procalcitonin levels (p < 0.001) also could distinguish a mild sepsis group from a severe sepsis and septic shock group. In a binary logistic regression model, only miR-499-5p and Sequential Organ Failure Assessment scores had good diagnostic values to distinguish between mild sepsis and severe sepsis and septic shock. CONCLUSION Four serum miRNAs were identified as novel biomarkers of sepsis. LEVEL OF EVIDENCE II, diagnostic study.

Journal ArticleDOI
01 Jun 2012-Chest
TL;DR: Different inflammatory patterns elicited by different microorganisms may provide a useful tool for diagnosis in community-acquired pneumonia, and recognizing these patterns provides additional information that may facilitate a broader understanding of host inflammatory response to microorganisms.

Journal ArticleDOI
TL;DR: Bacterial infections are common cause of morbidity and mortality in patients with cirrhosis and the early diagnosis of these infections is rather difficult.
Abstract: Background Bacterial infections are common cause of morbidity and mortality in patients with cirrhosis. The early diagnosis of these infections is rather difficult. Aims To assess the accuracy of acute phase proteins in the identification of bacterial infections. Methods Concentration of C-reactive protein (CRP), procalcitonin (PCT), lipopolysaccharide-binding protein (LBP), sCD14 and antimicrobial antibodies were measured in serum of 368 well-characterized patients with cirrhosis of whom 139 had documented infection. Clinical data was gathered by reviewing the patients’ medical charts. Results Serum levels of CRP, PCT and LBP were significantly higher in patients with clinically overt infections. Among the markers, CRP – using a 10 mg/L cut-off value– proved to be the most accurate in identifying patients with infection (AUC: 0.93). The accuracy of CRP, however, decreased in advanced stage of the disease, most probably because of the significantly elevated CRP levels in non-infected patients. Combination of CRP and PCT increased the sensitivity and negative predictive value, compared with CRP on its own, by 10 and 5% respectively. During a 3-month follow-up period in patients without overt infections, Kaplan–Meier and proportional Cox-regression analyses showed that a CRP value of >10 mg/L (P = 0.035) was independently associated with a shorter duration to progress to clinically significant bacterial infections. There was no correlation between acute phase protein levels and antimicrobial seroreactivity. Conclusions C-reactive protein on its own is a sensitive screening test for the presence of bacterial infections in cirrhosis and is also a useful marker to predict the likelihood of clinically significant bacterial infections in patients without overt infections.


Journal ArticleDOI
TL;DR: The combination of IL-6, hs-CRP, and PCT seems to be predictive in diagnosis of early onset neonatal sepsis.
Abstract: Neonatal sepsis is a major cause of morbidities and mortalities mostly remarkable in the third world nations We aimed to assess the value of simultaneous measurement of procalcitonin (PCT) and interleukin-6 (IL-6) in association with high sensitive- C reactive protein in prediction of early neonatal sepsis We performed a follow- up study on 95 neonates who were below 12 hours (h) of age, had clinical signs of sepsis or maternal risk factors for sepsis Neonates were assigned to 4 groups including “proven early-onset sepsis”, “clinical early-onset sepsis”, “negative infectious status”, and “uncertain infectious status” Blood samples were obtained within the first 12 h of birth repeated between 24 hours and 36 hours of age for determination of serum levels of PCT, IL-6, high sensitivie- C Reactive Protein (hs-CRP), and white blood cell (WBC) count On admission, neonates with sepsis had a higher WBC count, IL-6, PCT, and hs-CRP levels compared with those neonates without sepsis This remained significant even after 12-24 hours of admission Also, patients with clinical evidences of sepsis had a higher serum level of PCT and IL-6 within 12-24 hours after admission compared to the patients with uncertain sepsis In final The combination of IL-6, hs-CRP, and PCT seems to be predictive in diagnosis of early onset neonatal sepsis

Journal ArticleDOI
TL;DR: Genome-wide expression analysis has provided the foundation for the identification of IL-27 as a novel candidate diagnostic biomarker for predicting bacterial infection in critically ill children.
Abstract: Differentiating between sterile inflammation and bacterial infection in critically ill patients with fever and other signs of the systemic inflammatory response syndrome (SIRS) remains a clinical challenge. The objective of our study was to mine an existing genome-wide expression database for the discovery of candidate diagnostic biomarkers to predict the presence of bacterial infection in critically ill children. Genome-wide expression data were compared between patients with SIRS having negative bacterial cultures (n = 21) and patients with sepsis having positive bacterial cultures (n = 60). Differentially expressed genes were subjected to a leave-one-out cross-validation (LOOCV) procedure to predict SIRS or sepsis classes. Serum concentrations of interleukin-27 (IL-27) and procalcitonin (PCT) were compared between 101 patients with SIRS and 130 patients with sepsis. All data represent the first 24 hours of meeting criteria for either SIRS or sepsis. Two hundred twenty one gene probes were differentially regulated between patients with SIRS and patients with sepsis. The LOOCV procedure correctly predicted 86% of the SIRS and sepsis classes, and Epstein-Barr virus-induced gene 3 (EBI3) had the highest predictive strength. Computer-assisted image analyses of gene-expression mosaics were able to predict infection with a specificity of 90% and a positive predictive value of 94%. Because EBI3 is a subunit of the heterodimeric cytokine, IL-27, we tested the ability of serum IL-27 protein concentrations to predict infection. At a cut-point value of ≥5 ng/ml, serum IL-27 protein concentrations predicted infection with a specificity and a positive predictive value of >90%, and the overall performance of IL-27 was generally better than that of PCT. A decision tree combining IL-27 and PCT improved overall predictive capacity compared with that of either biomarker alone. Genome-wide expression analysis has provided the foundation for the identification of IL-27 as a novel candidate diagnostic biomarker for predicting bacterial infection in critically ill children. Additional studies will be required to test further the diagnostic performance of IL-27. The microarray data reported in this article have been deposited in the Gene Expression Omnibus under accession number GSE4607.

Journal ArticleDOI
TL;DR: The hypothesis of performing a randomised trial using a sputum purulence-guided antibiotic treatment strategy in patients with acute exacerbations of COPD supports the hypothesis that CRP, but not PCT, may be a useful parameter to increase confidence of the absence of bacterial bronchial infection.
Abstract: In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) needing hospitalisation, sputum purulence is associated with bacteria in the lower respiratory tract. We performed a prospective non-randomised interventional pilot study applying a sputum purulence-guided strategy of antibiotic treatment and investigating the relationship between sputum purulence and biomarkers. In hospitalised patients with acute exacerbation of COPD antibiotics were restricted to those with purulent sputum. The primary end-point was rate of therapeutic failure during hospitalisation. Secondary end-points were parameters reflecting short- and long-term outcomes. We included 73 patients, 34 with non-purulent sputum. No differences were observed on therapeutic failure criteria (9% non-purulent versus 10% purulent (p=0.51)). Serum C-reactive protein (CRP) was significantly increased in the purulent group at admission (11.6 versus 5.3, p=0.006) and at day 3 (2.7 versus 1.2, p=0.01). Serum procalcitonin (PCT) was similar between the groups. No differences were found in short-term outcomes. The exacerbation rate at 180 days was higher in the purulent group. These results support the hypothesis of performing a randomised trial using a sputum purulence-guided antibiotic treatment strategy in patients with acute exacerbations of COPD. CRP, but not PCT, may be a useful parameter to increase confidence of the absence of bacterial bronchial infection.

Journal ArticleDOI
01 Apr 2012-Chest
TL;DR: Recent evidence about the usefulness of procalcitonin (PCT) in patients with lower respiratory tract infections is summarized and the potential benefits and limitations of this marker when used for clinical decision making are discussed.

Journal ArticleDOI
01 May 2012-Burns
TL;DR: The maximum procalcitonin level has prognostic value in burn patients and can be used as a diagnostic tool in patients with infectious complications with or without bacteremia during ICU stay, which may be a valuable tool in monitoring the effectiveness of antibiotic therapy in burn ICU patients.

Journal ArticleDOI
31 Oct 2012-PLOS ONE
TL;DR: The combination of the biomarkers WBC, CRP and copeptin showed a better predictive accuracy concerning the development of pneumonia during hospitalization compared to each marker by itself, and the combination of these biomarkers improved the prediction of patients who developed an infection.
Abstract: Background Early predictors for the development of stroke-associated infection may identify patients at high risk and reduce post-stroke infection and mortality.

Journal ArticleDOI
TL;DR: Serial postoperative PCT measurements do not offer an advantage over CRP measurements for prediction of infectious complications following colorectal surgery.
Abstract: Colorectal surgery leads to high rates of postoperative complications, varying between 28% and 38% (1-3). Early diagnosis and prompt treatment of complications is crucial for a favorable outcome. However, surgical trauma induces systemic inflammatory response syndrome (SIRS), which can hinder the diagnosis of postoperative infections (4). Therefore, it would be useful to find a biochemical marker that could accurately differentiate between infectious and non-infectious SIRS. C-reactive protein (CRP), the first of the acute phase proteins to be described, was discovered in 1930 and named for its capacity to precipitate a non-protein somatic fraction (Fraction C) of Streptococcus pneumoniae. It is a sensitive systemic marker of inflammation and tissue damage, but is not specific for infection (5,6). Surgical trauma induces a significant increase in CRP levels, which can reduce its predictive value for the diagnosis of infection in the early postoperative period (7-9). Despite this, an interest in CRP as an infection monitoring tool in the perioperative setting has increased since it was reported that in values higher than 140 mg/L on the postopertaive day (POD) 3-4 it well predicted infectious complications after colorectal surgery (10). Since then, several studies have found it to be a useful predictor of septic complications following colorectal and esophagogastric resections (11-15). Procalcitonin (PCT), the prohormone of calcitonin, was first described as a biochemical marker of infection in 1993 (16). Bacterial endotoxins are potent stimuli for PCT synthesis, which exhibits faster kinetics than CRP. PCT is released into the circulation 3-4 hours after an injection of endotoxin, reaching peak levels after 8-24 hours, while CRP peaks at 36-50 hours after stimulus (5,17). This would make PCT more suitable as an infection monitoring tool in the perioperative setting (18,19). A meta analysis of 33 studies, which included adults in intensive care units or after surgery and trauma, showed that PCT was a good diagnostic marker of sepsis, with greater diagnostic accuracy than CRP (20). Recent studies in surgical patients have also shown that after orthopedic, cardiac, and thoracic surgery PCT was better for detecting postoperative infections than CRP (21-23). To the best of our knowledge, no studies have compared the diagnostic accuracy of CRP and PCT for early detection of postoperative complications in patients undergoing colorectal surgery. The aim of this study was to assess the predictive value of serial postoperative determinations of CRP, PCT, and white blood cell (WBC) count for infectious complications after elective colorectal surgery and to compare the diagnostic accuracy of CRP and PCT.