scholarly journals Clinical research assessment by flow cytometry of biomarkers for infectious stratification in an Emergency Department

2019 ◽  
Vol 13 (16) ◽  
pp. 1373-1386 ◽  
Author(s):  
Pénélope Bourgoin ◽  
Thomas Soliveres ◽  
Dalia Ahriz ◽  
Isabelle Arnoux ◽  
Christian Meisel ◽  
...  

Aim: Management of patients with infections within the Emergency Department (ED) is challenging for practitioners, as the identification of infectious causes remains difficult with current techniques. A new combination of two biomarkers was tested with a new rapid flow cytometry technique. Materials & methods: Subjects from the ED were tested for their CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169) levels and results were compared to their clinical records. Results: Among 139 patients, 29% had confirmed bacterial infections and 5% viral infections. nCD64 and mCD169 respectively showed 88 and 86% sensitivity and 90 and 100% specificity for identifying subjects in bacterial or viral conditions. Conclusion: This point-of-care technique could allow better management of patients in the ED.

2020 ◽  
Author(s):  
Pénélope Bourgoin ◽  
Thomas Soliveres ◽  
Alexandra Barbaresi ◽  
Anderson Loundou ◽  
Isabelle Arnoux ◽  
...  

ABSTRACTBackgroundThe identification of a bacterial, viral or even non-infectious cause is essential in the management of febrile syndrome in the emergency department (ED) setting, especially in epidemic contexts such as flu or CoVID-19.ObjectivesThe aim of this study was to assess discriminative performances of two biomarkers, CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169), using a new flow cytometry procedure, in patients presenting with fever to the ED. Human leucocyte antigen-DR on monocytes (mHLA-DR), HLA-ABC ratio (rHLA-ABC), and CD64 on monocytes (mCD64) were also assessed.Methods85 adult patients presenting with potential infection were included during the 2019 flu season in the ED of La Timone Hospital. They were divided into four diagnostic outcomes according to their clinical records: no-infection, bacterial infection, viral infection and co-infection.ResultsmCD169 was elevated in patients suffering from Flu A virus or Respiratory Syncytial Virus, while nCD64 was mainly found elevated in subjects with Streptococcus pneumoniae. In total, 38 (45%) patients were diagnosed with bacterial infections, 11 (13%) with viral infections and 29 (34%) with co-infections. nCD64 and mCD169 showed 90% and 80% sensitivity, and 78% and 91% specificity, respectively, for identifying patients with bacterial or viral infections. Other biomarkers had lower discriminative performances.ConclusionsnCD64 and mCD169 have potential for accurately distinguishing bacterial and acute viral infections. Combined in an easy and rapid flow cytometry procedure, they constitute a potential improvement for infection management in the ED setting, and could even help for the triage of patients during emerging epidemics.


2020 ◽  
Vol 15 (3) ◽  
pp. 189-201 ◽  
Author(s):  
Pénélope Bourgoin ◽  
Guillaume Lediagon ◽  
Isabelle Arnoux ◽  
Denis Bernot ◽  
Pierre-Emmanuel Morange ◽  
...  

Aim: In an Emergency Department (ED), the etiological identification of infected subjects is essential. 13 infection-related biomarkers were assessed using a new flow cytometry procedure. Materials & methods: If subjects presented with febrile symptoms at the ED, 13 biomarkers’ levels, including CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169), were tested and compared with clinical records. Results: Among 50 subjects, 78% had bacterial infections and 8% had viral infections. nCD64 showed 82% sensitivity and 91% specificity for identifying subjects with bacterial infections. mCD169, HLA-ABC ratio and HLA-DR on monocytes had high values in subjects with viral infections. Conclusion: Biomarkers showed promising performances to improve the ED's infectious stratification.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Christina A. Rostad ◽  
Neena Kanwar ◽  
Jumi Yi ◽  
Claudia R. Morris ◽  
Jennifer Dien Bard ◽  
...  

Abstract Background Fever is a common symptom in children presenting to the Emergency Department (ED). We aimed to describe the epidemiology of systemic viral infections and their predictive values for excluding serious bacterial infections (SBIs), including bacteremia, meningitis and urinary tract infections (UTIs) in children presenting to the ED with suspected systemic infections. Methods We enrolled children who presented to the ED with suspected systemic infections who had blood cultures obtained at seven healthcare facilities. Whole blood specimens were analyzed by an experimental multiplexed PCR test for 7 viruses. Demographic and laboratory results were abstracted. Results Of the 1114 subjects enrolled, 245 viruses were detected in 224 (20.1%) subjects. Bacteremia, meningitis and UTI frequency in viral bloodstream-positive patients was 1.3, 0 and 10.1% compared to 2.9, 1.3 and 9.7% in viral bloodstream-negative patients respectively. Although viral bloodstream detections had a high negative predictive value for bacteremia or meningitis (NPV = 98.7%), the frequency of UTIs among these subjects remained appreciable (9/89, 10.1%) (NPV = 89.9%). Screening urinalyses were positive for leukocyte esterase in 8/9 (88.9%) of these subjects, improving the ability to distinguish UTI. Conclusions Viral bloodstream detections were common in children presenting to the ED with suspected systemic infections. Although overall frequencies of SBIs among subjects with and without viral bloodstream detections did not differ significantly, combining whole blood viral testing with urinalysis provided high NPV for excluding SBI.


2015 ◽  
Vol 22 (9) ◽  
pp. 1025-1032 ◽  
Author(s):  
Per Venge ◽  
Lena Douhan-Håkansson ◽  
Daniel Garwicz ◽  
Christer Peterson ◽  
Shengyuan Xu ◽  
...  

ABSTRACTThe distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl-methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P< 0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P< 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP-activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.


2021 ◽  
Vol 8 ◽  
Author(s):  
Alejandra Comins-Boo ◽  
Maria Gutiérrez-Larrañaga ◽  
Adriel Roa-Bautista ◽  
Sandra Guiral Foz ◽  
Mónica Renuncio García ◽  
...  

Objectives: Several parameters aid in deciphering between viral and bacterial infections; however, new tools should be investigated in order to reduce the time to results and proceed with an early target-therapy. Validation of a biomarker study, including CD64 and CD169 expression, was conducted.Material and Methods: Patients with active SARS-CoV-2 infection (ACov-2), bacterial infection (ABI), healthy controls, and antiretroviral-controlled chronic HIV infection were assessed. Whole blood was stained and, after lysing no-wash protocol, acquired by flow cytometry. The median fluorescence intensity (MFI) of CD64 and CD169 was measured in granulocytes, monocytes, and lymphocytes. The CD64 MFI ratio granulocytes to lymphocytes (CD64N) and CD169 MFI ratio monocytes to lymphocytes (CD169Mo) were evaluated as biomarkers of acute bacterial and viral infection, respectively.Results: A CD64N ratio higher than 3.3 identified patients with ABI with 83.3 and 85.9% sensitivity and specificity, with an area under the curve (AUC) of 83.5%. In contrast, other analytic or hematological parameters used in the clinic had lower AUC compared with the CD64N ratio. Moreover, a CD169Mo ratio higher than 3.3 was able to identify ACov-2 with 91.7 and 89.8 sensitivity and specificity, with the highest AUC (92.0%).Conclusion: This work confirms the previous data of CD64N and CD169Mo ratios in an independent cohort, including controlled chronic viral HIV infection patients as biomarkers of acute bacterial and viral infections, respectively. Such an approach would benefit from quick pathogen identification for a direct-therapy with a clear application in different Health Care Units, especially during this COVID pandemic.


2020 ◽  
Author(s):  
Asimina Safarika ◽  
James W. Wacker ◽  
Konstantinos Katsaros ◽  
Nicky Solomonidi ◽  
George Giannikopoulos ◽  
...  

AbstractStudy designWhether or not to administer antibiotics is a common and challenging clinical decision in patients with suspected infections presenting to the emergency department (ED). We prospectively validate InSep, a 29-mRNA blood-based host response test for the prediction of bacterial and viral infections.MethodsThe PROMPT trial is a prospective, non-interventional, multi-center randomized, controlled clinical trial that enrolled 397 adult patients presenting to the ED with signs of acute infection and at least one vital sign change. The infection status was adjudicated using chart review (including a syndromic molecular respiratory panel, procalcitonin and C-reactive protein) by three infectious disease physicians blinded to InSep results. InSep (version BVN-2) was performed using PAXgene Blood RNA processed and quantified on NanoString nCounter SPRINT. InSep results (likelihood of bacterial and viral infection) were compared to the adjudicated infection status.ResultsSubject mean age was 64 years, comorbidities were significant for diabetes (17.1%), chronic obstructive pulmonary disease (13.6%), and severe neurological disease (6.8%); 16.9% of subjects were immunocompromised. Infections were adjudicated as bacterial (14.1%), viral (11.3%) and noninfected (0.25%): 74.1% of subjects were adjudicated as indeterminate. InSep distinguished bacterial vs. viral/noninfected patients and viral vs. bacterial/noninfected patients using consensus adjudication with AUROCs of 0.94 (95% CI 0.90-0.99) and 0.90 (95% CI 0.83-0.96), respectively. AUROCs for bacterial vs. viral/noninfected patients were 0.88 (95%CI 0.79-0.96) for PCT, 0.80 (95% CI 0.72-89) for CRP and 0.78 (95% CI 0.69-0.87) for white blood cell counts (of note, the latter biomarkers were provided as part of clinical adjudication). To enable clinical actionability, InSep incorporates score cutoffs to allocate patients into interpretation bands. The Very Likely (rule in) InSep bacterial band showed a specificity of 98% compared to 94% for the corresponding PCT band (>0.5 ug/L); the Very Unlikely (rule-out) band showed a sensitivity of 95% for InSep compared to 86% for PCT. For the detection of viral infections, InSep demonstrated a specificity of 93% for the Very Likely band (rule in) and a sensitivity of 96% for the Very Unlikely band (rule out).ConclusionInSep demonstrated high accuracy for predicting the presence of both bacterial and viral infections in ED patients with suspected acute infections or suspected sepsis. When translated into a rapid, point-of-care test, InSep will provide ED physicians with actionable results supporting early informed treatment decisions to improve patient outcomes while upholding antimicrobial stewardship.Take-home messageInSep host response test is a point-of-care test providing with accuracy the likelihood for bacterial or viral infection for patients admitted at the emergencies InSep provided information on the likelihood of bacterial co-infection among patients with COVID-19.


2019 ◽  
pp. 189-211
Author(s):  
Leah Bauer ◽  
Carolyn Chooljian ◽  
Whitney Johnson

Generalized complaints such as fever, chills, malaise, and body aches are common presentations to the emergency department (ED). Some of these are due to viral infections, and some are due to systemic bacterial infections. Clues to the specific infection can be found in the geographic location of the patient or the patient’s exposure to wildlife (e.g., ticks) and animals. The patient’s history and the timing of the illness play an important part in helping to identify the possible source or cause of the infection. This chapter presents questions related to the diagnosis, clinical effects, and most appropriate treatment of a wide range of these systemic infectious disease emergencies.


2018 ◽  
Author(s):  
Samuel Arthur Rhedin ◽  
Annika Eklundh ◽  
Malin Ryd-Rinder ◽  
Pontus Naucler ◽  
Andreas Mårtensson ◽  
...  

BACKGROUND There is a need to better distinguish viral infections from antibiotic-requiring bacterial infections in children presenting with clinical community-acquired pneumonia (CAP) to assist health care workers in decision making and to improve the rational use of antibiotics. OBJECTIVE The overall aim of the Trial of Respiratory infections in children for ENhanced Diagnostics (TREND) study is to improve the differential diagnosis of bacterial and viral etiologies in children aged below 5 years with clinical CAP, by evaluating myxovirus resistance protein A (MxA) as a biomarker for viral CAP and by evaluating an existing (multianalyte point-of-care antigen detection test system [mariPOC respi] ArcDia International Oy Ltd.) and a potential future point-of-care test for respiratory pathogens. METHODS Children aged 1 to 59 months with clinical CAP as well as healthy, hospital-based, asymptomatic controls will be included at a pediatric emergency hospital in Stockholm, Sweden. Blood (analyzed for MxA and C-reactive protein) and nasopharyngeal samples (analyzed with real-time polymerase chain reaction as the gold standard and antigen-based mariPOC respi test as well as saved for future analyses of a novel recombinase polymerase amplification–based point-of-care test for respiratory pathogens) will be collected. A newly developed algorithm for the classification of CAP etiology will be used as the reference standard. RESULTS A pilot study was performed from June to August 2017. The enrollment of study subjects started in November 2017. Results are expected by the end of 2019. CONCLUSIONS The findings from the TREND study can be an important step to improve the management of children with clinical CAP. INTERNATIONAL REGISTERED REPOR DERR1-10.2196/12705


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-9
Author(s):  
Satish Maharaj ◽  
Simone Chang ◽  
Karan Seegobin ◽  
Marwan Shaikh ◽  
Kamila I. Cisak

Background: Patients with sickle cell disease (SCD) are at increased risk of developing bacterial infections as a result of functional asplenia. Fever, a common symptom in SCD often occurs with other sickle cell related conditions and viral infections. This poses a diagnostic challenge and early use of empiric antibiotics is recommended while awaiting cultures. The widespread administration of antibiotics to all patients with SCD with fever can result in problems such as antibiotic resistance and increased medical costs. An early and reliable biomarker is therefore needed to help distinguish between bacterial and non-bacterial causes for fever in SCD. Procalcitonin (PCT) has been shown to be elevated in bacterial but not viral infections. In SCD, few studies have looked at the role of PCT in predicting bacterial infections. Unal et al reported vaso-occlusive crisis (VOC) with or without fever did not increase PCT levels in relation to patients with no crisis and no fever. However, Rincón-López et al reported a PCT &lt; 0.6ng/mL had a negative predictive value of 97.2% and potentially could be used to identify bacterial infection early. Methods: We retrospectively studied 122 patients with SCD who presented to the emergency department with fever from 2015-2019. Inclusion criteria were defined as patients with SCD, 17 years and older and PCT measurement on presentation to the emergency department. Exclusion criteria were defined as patients with SCD and fever who had received empiric antibiotics prior to labs being drawn in the emergency department. The cohort was divided into groups of patients with Confirmed Bacterial Infection (CBI, n=18), Suspected Bacterial Infection (SBI, n=6), Viral Infections (n=10) and Vaso-Occlusive Crises (VOC, n=88) only. CBI was defined as a positive bacterial culture (blood, body fluid, urine, respiratory or cerebrospinal fluid) or C.difficile toxin assay. Viral infections were defined as a negative bacterial culture in the presence of a virus found on PCR obtained with nasopharyngeal swab. Characteristics including genotype, age, gender, complete blood count, PCT, creatinine, total bilirubin, hydroxyurea use and length of stay were examined. Data was analyzed between the groups using descriptive statistics and accounting for unequal variances, with p-value set at 0.05 for significance. Results: Demographics and clinical characteristics are summarized in Table 1 (Figure). The mean age was 34.6 years with predominantly males (64.8%). Almost two-thirds were on hydroxyurea (62.3%). The most common genotype was HbSS (70.5%) followed by HbSC (26.2%) and HbSβ (3.3%). The mean PCT for patients with CBI was 8.99 ng/mL (range, 0.03-78.36) as compared to 0.31 ng/mL (range, 0.02-6.82) in the VOC group. The most common organisms detected were E.coli, C.difficile, Pseudomonas, Staphylococcus and Enterobacter. There was a significant difference between median PCT for patients with CBI and those with VOC (p=0.036) and between patients with CBI and viral infections (p= 0.045). Using a PCT of &gt;0.5ng/mL resulted in 81% Sensitivity and 85% Specificity for CBI. Conclusion: In patients with SCD presenting with fever, PCT on presentation was significantly higher in those with CBI compared to VOC only or Viral Infection. Disclosures No relevant conflicts of interest to declare.


Sign in / Sign up

Export Citation Format

Share Document