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C-reactive protein, an early marker of community-acquired sepsis resolution: a multi-center prospective observational study.

ABSTRACT: INTRODUCTION: C-reactive protein (CRP) has been shown to be a valuable marker in the diagnosis of infection and in monitoring its response to antibiotics. Our objective was to evaluate serial CRP measurements after prescription of antibiotics to describe the clinical course of Community-Acquired Sepsis admitted to intensive care units (ICU). METHODS: During a 12-month period a multi-center, prospective, observational study was conducted, segregating adults with Community-Acquired Sepsis. Patients were followed-up during the first five ICU days, day of ICU discharge or death and hospital outcome. CRP-ratio was calculated in relation to Day 1 CRP concentration. Patients were classified according to the pattern of CRP-ratio response to antibiotics: fast response if Day 5 CRP-ratio was < 0.4, slow response if Day 5 CRP-ratio was between 0.4 and 0.8, and no response if Day 5 CRP-ratio was > 0.8. Comparison between survivors and non-survivors was performed. RESULTS: A total of 891 patients (age 60 ± 17 yrs, hospital mortality 38%) were studied. There were no significant differences between the CRP of survivors and non-survivors until Day 2 of antibiotic therapy. On the following three days, CRP of survivors was significantly lower (P < 0.001). After adjusting for the Simplified Acute Physiology Score II and severity of sepsis, the CRP course was significantly associated with mortality (ORCRP-ratio = 1.03, confidence interval 95%= (1.02, 1.04), P < 0.001). The hospital mortality of patients with fast response, slow response and no response patterns was 23%, 30% and 41%, respectively (P = 0.001). No responders had a significant increase on the odds of death (OR = 2.5, CI95% = (1.6, 4.0), P < 0.001) when compared with fast responders. CONCLUSIONS: Daily CRP measurements after antibiotic prescription were useful as early as Day 3 in identification of Community-Acquired Sepsis patients with poor outcome. The rate of CRP decline during the first five ICU days was markedly associated with prognosis. The identification of the pattern of CRP-ratio response was useful in the recognition of the individual clinical course.

SUBMITTER: Povoa P

PROVIDER: S-EPMC3387609 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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C-reactive protein, an early marker of community-acquired sepsis resolution: a multi-center prospective observational study.

Póvoa Pedro P Teixeira-Pinto Armando M AM Carneiro António H AH

Critical care (London, England) 20110715 4

<h4>Introduction</h4>C-reactive protein (CRP) has been shown to be a valuable marker in the diagnosis of infection and in monitoring its response to antibiotics. Our objective was to evaluate serial CRP measurements after prescription of antibiotics to describe the clinical course of Community-Acquired Sepsis admitted to intensive care units (ICU).<h4>Methods</h4>During a 12-month period a multi-center, prospective, observational study was conducted, segregating adults with Community-Acquired Se ...[more]

PMID: 21762483

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Project description:BackgroundCommunity acquired pneumonia (CAP) is a high incidence disease resulting in about 260,000 hospital admissions per year in Germany, more than myocardial infarction or stroke. Worldwide, CAP is the most frequent infectious disease with high lethality ranging from 1.2 % in those 20-29 years old to over 10 % in patients older than 70 years, even in industrial nations. CAP poses numerous medical challenges, which the PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) network aims to tackle: Operationalization of disease severity throughout the course of disease, outcome prediction for hospitalized patients and prediction of transitions from uncomplicated CAP to severe CAP, and finally, to CAP with sepsis and organ failure as a life-threatening condition. It is a major aim of PROGRESS to understand and predict patient heterogeneity regarding outcome in the hospital and to develop novel treatment concepts.MethodsPROGRESS was designed as a clinical, observational, multi-center study of patients with CAP requiring hospitalization. More than 1600 patients selected for low burden of co-morbidities have been enrolled, aiming at a total of 3000. Course of disease, along with therapy, was closely monitored by daily assessments and long-term follow-up. Daily blood samples allow in depth molecular-genetic characterization of patients. We established a well-organized workflow for sample logistics and a comprehensive data management system to collect and manage data from more than 50 study centers in Germany and Austria. Samples are stored in a central biobank and clinical data are stored in a central data base which also integrates all data from molecular assessments.DiscussionWith the PROGRESS study, we established a comprehensive data base of high quality clinical and molecular data allowing investigation of pressing research questions regarding CAP. In-depth molecular characterization will contribute to the discovery of disease mechanisms and establishment of diagnostic and predictive biomarkers. A strength of PROGRESS is the focus on younger patients with low burden of co-morbidities, allowing a more direct look at host biology with less confounding. As a resulting limitation, insights from PROGRESS will require validation in representative patient cohorts to assess clinical utility.Trial registrationThe PROGRESS study was retrospectively registered on May 24(th), 2016 with ClinicalTrials.gov: NCT02782013.

Project description:BACKGROUND:T helper (Th) cells regulate sepsis processes, including primary pathogen clear and secondary pathogen defence. The objectives of this study were to determine the early and dynamic alterations of Th1 and Th2 populations to community-acquired severe sepsis upon onset among previously immunocompetent patients and whether it was related to clinical outcomes. METHODS:This prospective observational cohort study was conducted at a general intensive care unit (ICU) of a tertiary teaching hospital in China. Immunocompetent patients with community-acquired severe sepsis within 24 h upon onset were included as septic group. Healthy volunteers and critically ill patients without severe sepsis were recruited as controls. Whole blood was collected on D0, 3rd day (D3) and 7th day (D7) for septic group and once upon enrollment for controls. Th1 and Th2 populations were measured by flow cytometry and assessed for associations with 28-day mortality using cox proportional hazard models. Associations of dynamic alterations of Th cell subpopulations with clinical outcomes were investigated. RESULTS:This study demonstrated that community-acquired severe sepsis patients (n = 71) had increased Th2/Th1 and Th2 populations, compared to healthy controls (n = 7) and critically ill patients without severe sepsis (n = 7) at admission. Among the septic cohort, values of Th2/Th1 were significantly higher in non-survivors than survivors on D0 (p = 0.04), D3 (p < 0.001) and D7 (p < 0.001). Patients with persistently increasing Th2/Th1 demonstrated the highest mortality (47.1%) and incidence of ICU-acquired infections (64.7%). CONCLUSIONS:Th2/Th1 was markedly up-regulated with Th2 dominance upon community-acquired severe sepsis onset among previously immunocompetent patients and its persistently dynamic increase was associated with ICU-acquired infections and 28-day death. Trial registration Institutional Ethics Committee of Zhongda Hospital, 2014ZDSYLL086, registered in June 2014-prospectively registered; ClinicalTrials.gov, NCT02883218, registered on 25 Aug 2016-retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02883218?cond=NCT02883218&rank=1.

Project description:Infection and sepsis are leading causes of death worldwide but the epidemiology and outcomes are not well understood in resource-limited settings. We conducted a four-year prospective observational study from March 2013 to February 2017 to examine the clinical epidemiology and outcomes of adults admitted with community-acquired infection in a resource-limited tertiary-care hospital in Ubon Ratchathani province, Northeast Thailand. Hospitalized patients with infection and accompanying systemic manifestations of infection within 24 hours of admission were enrolled. Subjects were classified as having sepsis if they had a modified sequential organ failure assessment (SOFA) score ≥2 at enrollment. This study was registered with ClinicalTrials.gov, number NCT02217592. A total of 4,989 patients were analyzed. Of the cohort, 2,659 (53%) were male and the median age was 57 years (range 18-101). Of these, 1,173 (24%) patients presented primarily to the study hospital, 3,524 (71%) were transferred from 25 district hospitals or 8 smaller hospitals in the province, and 292 (6%) were transferred from one of 30 hospitals in other provinces. Three thousand seven hundred and sixteen (74%) patients were classified as having sepsis. Patients with sepsis had an older age distribution and a greater prevalence of comorbidities compared to patients without sepsis. Twenty eight-day mortality was 21% (765/3,716) in sepsis and 4% (54/1,273) in non-sepsis patients (p<0.001). After adjusting for gender, age, and comorbidities, sepsis on admission (adjusted hazard ratio [HR] 3.30; 95% confidence interval [CI] 2.48-4.41, p<0.001), blood culture positive for pathogenic organisms (adjusted HR 2.21; 95% CI 1.89-2.58, p<0.001) and transfer from other hospitals (adjusted HR 2.18; 95% CI 1.69-2.81, p<0.001) were independently associated with mortality. In conclusion, mortality of community-acquired sepsis in Northeast Thailand is considerable and transferred patients with infection are at increased risk of death. To reduce mortality of sepsis in this and other resource-limited setting, facilitating rapid detection of sepsis in all levels of healthcare facilities, establishing guidelines for transfer of sepsis patients, and initiating sepsis care prior to and during transfer may be beneficial.

Project description:BackgroundProgranulin is a widely expressed pleiotropic growth factor with a central regulatory effect during the early immune response in sepsis. Progranulin signaling has not been systematically studied and compared between sepsis, community-acquired pneumonia (CAP), COVID-19 pneumonia and a sterile systemic inflammatory response (SIRS). We delineated molecular networks of progranulin signaling by next-generation sequencing (NGS), determined progranulin plasma concentrations and quantified the diagnostic performance of progranulin to differentiate between the above-mentioned disorders using the established biomarkers procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) for comparison.MethodsThe diagnostic performance of progranulin was operationalized by calculating AUC and ROC statistics for progranulin and established biomarkers in 241 patients with sepsis, 182 patients with SIRS, 53 patients with CAP, 22 patients with COVID-19 pneumonia and 53 healthy volunteers. miRNAs and mRNAs in blood cells from sepsis patients (n = 7) were characterized by NGS and validated by RT-qPCR in an independent cohort (n = 39) to identify canonical gene networks associated with upregulated progranulin at sepsis onset.ResultsPlasma concentrations of progranulin (ELISA) in patients with sepsis were 57.5 (42.8-84.9, Q25-Q75) ng/ml and significantly higher than in CAP (38.0, 33.5-41.0 ng/ml, p < 0.001), SIRS (29.0, 25.0-35.0 ng/ml, p < 0.001) and the healthy state (28.7, 25.5-31.7 ng/ml, p < 0.001). Patients with COVID-19 had significantly higher progranulin concentrations than patients with CAP (67.6, 56.6-96.0 vs. 38.0, 33.5-41.0 ng/ml, p < 0.001). The diagnostic performance of progranulin for the differentiation between sepsis vs. SIRS (n = 423) was comparable to that of procalcitonin. AUC was 0.90 (95% CI = 0.87-0.93) for progranulin and 0.92 (CI = 0.88-0.96, p = 0.323) for procalcitonin. Progranulin showed high discriminative power to differentiate bacterial CAP from COVID-19 (sensitivity 0.91, specificity 0.94, AUC 0.91 (CI = 0.8-1.0) and performed significantly better than PCT, IL-6 and CRP. NGS and partial RT-qPCR confirmation revealed a transcriptomic network of immune cells with upregulated progranulin and sortilin transcripts as well as toll-like-receptor 4 and tumor-protein 53, regulated by miR-16 and others.ConclusionsProgranulin signaling is elevated during the early antimicrobial response in sepsis and differs significantly between sepsis, CAP, COVID-19 and SIRS. This suggests that progranulin may serve as a novel indicator for the differentiation between these disorders.Trial registrationClinicaltrials.gov registration number NCT03280576 Registered November 19, 2015.

Project description:IntroductionWe aimed to facilitate the diagnosis and prognosis of sepsis-related organ dysfunction through analyzing presepsin (PSEP) and gelsolin (GSN) levels along with a novel marker, the presepsin:gelsolin (PSEP:GSN) ratio.MethodsBlood samples were collected from septic patients at the intensive care unit (ICU) at three time points (T1-3): T1: within 12 h after admission; T2: second day morning; T3: third day morning. Sampling points for non-septic ICU patients were T1 and T3. PSEP was measured by a chemiluminescence-based POCT method while GSN was determined by an automated immune turbidimetric assay. Data were compared with routine lab and clinical parameters. Patients were categorized by the Sepsis-3 definitions. PSEP:GSN ratio was evaluated in major sepsis-related organ dysfunctions including hemodynamic instability, respiratory insufficiency and acute kidney injury (AKI).ResultsIn our single center prospective observational study, 126 patients were enrolled (23 control, 38 non-septic and 65 septic patients). In contrast to controls, significantly elevated (p < 0.001) admission PSEP:GSN ratios were found in non-septic and septic patients. Regarding 10-day mortality prediction, PSEP:GSN ratios were lower (p < 0.05) in survivors than in non-survivors during follow-up, while the prognostic performance of PSEP:GSN ratio was similar to widely used clinical scores (APACHE II, SAPS II, SOFA). PSEP:GSN ratios were also higher (p < 0.001) in patients with sepsis-related AKI than septic non-AKI patients during follow-up, especially in sepsis-related AKI patients needing renal replacement therapy. Furthermore, increasing PSEP:GSN ratios were in good agreement (p < 0.001) with the dosage and the duration of vasopressor requirement in septic patients. Moreover, PSEP:GSN ratios were markedly greater (p < 0.001) in patients with septic shock than in septic patients without shock. Compared to septic patients requiring oxygen supplementation, substantially elevated (p < 0.001) PSEP:GSN ratios were observed in septic patients with demand for mechanical ventilation, while higher PSEP:GSN ratios (p < 0.001) were also associated with extended periods of mechanical ventilation requirement in septic patients.ConclusionPSEP:GSN ratio could be a useful complementary marker besides the routinely used SOFA score regarding the diagnosis and short term mortality prediction of sepsis. Furthermore, the significant increase of this biomarker may also indicate the need for prolonged vasopressor or mechanical ventilation requirement of septic patients. PSEP:GSN ratio could yield valuable information regarding the extent of inflammation and the simultaneous depletion of the patient's scavenger capacity during sepsis.Clinical trail registrationNIH U.S. National Library of Medicine, ClinicalTrails.gov. Trial identifier: NCT05060679, (https://clinicaltrials.gov/ct2/show/NCT05060679) 23.03.2022, Retrospectively registered.

Project description:Background:The burden of sepsis is highest in low- and middle-income countries, though the management of sepsis in these settings is poorly characterized. Therefore, the objective of this study was to assess the early management of sepsis in Thailand. Methods:Pre-planned analysis of the Ubon-sepsis study, a single-center prospective cohort study of Thai adults admitted to the general medical wards and medical intensive care units (ICUs) of a regional referral hospital with community-acquired sepsis. Results:Between March 2013 and January 2017, 3,716 patients with sepsis were enrolled. The median age was 59?years (IQR 44-72, range 18-101), 58% were male, and 88% were transferred from other hospitals. Eighty-six percent of patients (N = 3,206) were evaluated in the Emergency Department (ED), where median length of stay was less than 1?hour. Within the first day of admission, most patients (83%, N = 3,089) were admitted to the general medical wards, while 17% were admitted to the ICUs. Patients admitted to the ICUs had similar age, gender, and comorbidities, but had more organ dysfunction and were more likely to receive measured sepsis management interventions. Overall, 84% (N = 3,136) had blood cultures ordered and 89% (N = 3,308) received antibiotics within the first day of hospital admission. Among the 3,089 patients admitted to the general medical wards, 38% (N = 1,165) received an adrenergic agent, and 21% (N = 650) received invasive mechanical ventilation. Overall mortality at 28?days was 21% (765/3,716), and 28-day mortality in patients admitted to the ICUs was higher than that in patients admitted to the general medical wards within the first day (42% [263/627] vs. 16% [502/3,089], p < 0.001). Conclusions:Sepsis in a regional referral hospital in rural Thailand, where some critical care resources are limited, is commonly managed on general medical wards despite high rates of respiratory failure and shock. Enhancing sepsis care in the ED and general wards, as well as improving access to ICUs, may be beneficial in reducing mortality. Trial registration:The Ubon-sepsis study was registered on clinicaltrials.gov (NCT02217592).

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C-reactive protein, an early marker of community-acquired sepsis resolution: a multi-center prospective observational study.

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C-reactive protein, an early marker of community-acquired sepsis resolution: a multi-center prospective observational study.

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