Assessment of a Cellular Host Response Test as a Sepsis Diagnostic for Those With Suspected Infection in the Emergency Department

Abstract Background Whether 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. Methods The PROMPT trial is a prospective, non-interventional, multi-center clinical study 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. Results Subject 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 µg/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). Conclusions InSep 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. Registration number at Clinicaltrials.gov NCT 03295825.

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A 29-mRNA Host Response Test from Blood Accurately Distinguishes Bacterial and Viral Infections Among Emergency Department Patients

10.1101/2020.12.01.20242321 ◽

2020 ◽

Author(s):

Asimina Safarika ◽

James W. Wacker ◽

Konstantinos Katsaros ◽

Nicky Solomonidi ◽

George Giannikopoulos ◽

...

Keyword(s):

Emergency Department ◽

Viral Infection ◽

Host Response ◽

Viral Infections ◽

Point Of Care ◽

Infection Status ◽

Response Test ◽

Point Of Care Test ◽

Cell Counts ◽

Rule Out

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.

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Correlation of Quick SOFA Score and Procalcitonin with Mortality in the Emergency Department

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2020/v32i630434 ◽

2020 ◽

pp. 64-69

Author(s):

Mandip Singh Bhatia ◽

Ritu Attri ◽

Kumar Rajni Kant ◽

Saurabh C. Sharda

Keyword(s):

Emergency Department ◽

Early Diagnosis ◽

Organ Dysfunction ◽

Sofa Score ◽

Host Response ◽

Death Sentence ◽

Suspected Infection ◽

Life Threatening ◽

Qsofa Score ◽

Sensitive Marker

Introduction: Sepsis is defined as life-threatening organ dysfunction caused by the dysregulated host response to infection with high mortality. Early diagnosis and treatment can decrease mortality. Methods: We studied 2031 patients presenting to an emergency department with fever or suspected infection to find the correlation between q SOFA SCORE and procalcitonin levels with mortality. Results: It is seen that mortality is directly proportionate to qSofa score and we also found that the value of procalcitonin is directly proportionate to qSofa score. Conclusion: Combination of qSofa score with procalcitonin is a sensitive marker of death in sepsis. qSofa score of 2 or more is associated with increased mortality but its, not death sentence if all such patients treated aggressively & timely then the majority of them would survive.

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A 29-mRNA Host Response Test from Blood Accurately Distinguishes Bacterial and Viral Infections Among Emergency Department Patients

10.21203/rs.3.rs-128429/v1 ◽

2020 ◽

Author(s):

Asimina Safarika ◽

James W Wacker ◽

Konstantinos Katsaros ◽

Nicky Solomonidi ◽

George Giannikopoulos ◽

...

Keyword(s):

Emergency Department ◽

Host Response ◽

Viral Infections ◽

Acute Infection ◽

Controlled Clinical Trial ◽

Chronic Obstructive ◽

Suspected Sepsis ◽

Response Test ◽

Cell Counts ◽

Rule Out

Abstract BackgroundWhether 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). ConclusionsInSep 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. Registration number at Clinicaltrials.gov NCT 03295825

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24‐hour fluid administration in emergency department patients with suspected infection; a multicenter, prospective, observational study

Acta Anaesthesiologica Scandinavica ◽

10.1111/aas.13848 ◽

2021 ◽

Author(s):

Marie Kristine Jessen ◽

Lars Wiuff Andersen ◽

Marie‐Louise Holm Thomsen ◽

Marie Egebjerg Jensen ◽

Mathilde Emilie Kirk ◽

...

Keyword(s):

Emergency Department ◽

Observational Study ◽

Prospective Observational Study ◽

Fluid Administration ◽

Suspected Infection ◽

Multicenter Prospective Observational Study ◽

Emergency Department Patients

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The Feasibility and Accuracy of Point-of-Care Lactate Measurement in Emergency Department Patients with Suspected Infection

Journal of Emergency Medicine ◽

10.1016/j.jemermed.2009.07.021 ◽

2010 ◽

Vol 39 (1) ◽

pp. 89-94 ◽

Cited By ~ 44

Author(s):

Nathan I. Shapiro ◽

Christopher Fisher ◽

Michael Donnino ◽

Lauren Cataldo ◽

Aimee Tang ◽

...

Keyword(s):

Emergency Department ◽

Point Of Care ◽

Suspected Infection ◽

Lactate Measurement ◽

Emergency Department Patients

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Serum Lactate Is a Better Predictor of Short-Term Mortality When Stratified by C-reactive Protein in Adult Emergency Department Patients Hospitalized for a Suspected Infection

Annals of Emergency Medicine ◽

10.1016/j.annemergmed.2010.10.016 ◽

2011 ◽

Vol 57 (3) ◽

pp. 291-295 ◽

Cited By ~ 23

Author(s):

Jeffrey P. Green ◽

Tony Berger ◽

Nidhi Garg ◽

Nathan I. Shapiro

Keyword(s):

Emergency Department ◽

Serum Lactate ◽

C Reactive Protein ◽

Short Term ◽

Suspected Infection ◽

Reactive Protein ◽

Short Term Mortality ◽

Emergency Department Patients

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The REDS score: a new scoring system to risk-stratify emergency department suspected sepsis: a derivation and validation study

BMJ Open ◽

10.1136/bmjopen-2019-030922 ◽

2019 ◽

Vol 9 (8) ◽

pp. e030922 ◽

Cited By ~ 2

Author(s):

Narani Sivayoham ◽

Lesley A Blake ◽

Shafi E Tharimoopantavida ◽

Saad Chughtai ◽

Adil N Hussain ◽

...

Keyword(s):

Emergency Department ◽

High Risk ◽

Prediction Rule ◽

Clinical Prediction Rule ◽

Risk Category ◽

Suspected Sepsis ◽

Suspected Infection ◽

Derivation Cohort ◽

High Risk Category ◽

Component Scores

ObjectiveTo derive and validate a new clinical prediction rule to risk-stratify emergency department (ED) patients admitted with suspected sepsis.DesignRetrospective prognostic study of prospectively collected data.SettingED.ParticipantsPatients aged ≥18 years who met two Systemic Inflammatory Response Syndrome criteria or one Red Flag sepsis criteria on arrival, received intravenous antibiotics for a suspected infection and admitted.Primary outcome measureIn-hospital all-cause mortality.MethodThe data were divided into derivation and validation cohorts. The simplified-Mortality in Severe Sepsis in the ED score and quick-SOFA scores, refractory hypotension and lactate were collectively termed ‘component scores’ and cumulatively termed the ‘Risk-stratification of ED suspected Sepsis (REDS) score’. Each patient in the derivation cohort received a score (0–3) for each component score. The REDS score ranged from 0 to 12. The component scores were subject to univariate and multivariate logistic regression analyses. The receiver operator characteristic (ROC) curves for the REDS and the components scores were constructed and their cut-off points identified. Scores above the cut-off points were deemed high-risk. The area under the ROC (AUROC) curves and sensitivity for mortality of the high-risk category of the REDS score and component scores were compared. The REDS score was internally validated.Results2115 patients of whom 282 (13.3%) died in hospital. Derivation cohort: 1078 patients with 140 deaths (13%). The AUROC curve with 95% CI, cut-off point and sensitivity for mortality (95% CI) of the high-risk category of the REDS score were: derivation: 0.78 (0.75 to 0.80); ≥3; 85.0 (78 to 90.5). Validation: 0.74 (0.71 to 0.76); ≥3; 84.5 (77.5 to 90.0). The AUROC curve and the sensitivity for mortality of the REDS score was better than that of the component scores. Specificity and mortality rates for REDS scores of ≥3, ≥5 and ≥7 were 54.8%, 88.8% and 96.9% and 21.8%, 36.0% and 49.1%, respectively.ConclusionThe REDS score is a simple and objective score to risk-stratify ED patients with suspected sepsis.

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Cost Impact Model of a Novel Multi-mRNA Host Response Assay for Diagnosis and Risk Assessment of Acute Respiratory Tract Infections and Sepsis in the Emergency Department

Journal of Health Economics and Outcomes Research ◽

10.36469/jheor.2020.12637 ◽

2020 ◽

Vol 7 (1) ◽

pp. 24-34 ◽

Cited By ~ 1

Author(s):

John E. Schneider ◽

Jonathan Romanowsky ◽

Philipp Schuetz ◽

Ivana Stojanovic ◽

Henry K. Cheng ◽

...

Keyword(s):

Emergency Department ◽

Respiratory Tract ◽

Host Response ◽

Meta Analysis ◽

Standard Of Care ◽

Analysis Data ◽

Disease Prevalence ◽

Impact Model ◽

Cost Impact ◽

Tract Infections

Background: Early identification of acute infections and sepsis remains an unmet medical need. While early detection and initiation of treatment reduces mortality, inappropriate treatment leads to adverse events and the development of antimicrobial resistance. Current diagnostic and prognostic solutions, including procalcitonin, lack required accuracy. A novel blood-based host response test, HostDx™ Sepsis by Inflammatix, Inc., assesses the likelihood of a bacterial infection, the likelihood of a viral infection, and the severity of the condition. Objectives: We estimated the economic impact of adopting HostDx Sepsis testing among patients with suspected acute respiratory tract infection (ARTI) in the emergency department (ED). Methods: Our cost impact model estimated costs for adult ED patients with suspected ARTI under the standard of care versus with the adoption of HostDx Sepsis from the perspective of US payers. Included costs were those assumed to be associated with an episode of sepsis diagnosis, management, and treatment. Projected accuracies for test predictions, disease prevalence, and clinical parameters was derived from patient-level meta-analysis data of randomized trials, supplemented with published performance data for HostDx Sepsis. One-way sensitivity analysis was performed on key input parameters. Results: Compared to standard of care including procalcitonin, the superior test characteristics of HostDx Sepsis resulted in an average cost savings of approximately US$1974 per patient (-31.3%) exclusive of the cost of HostDx Sepsis. Reductions in hospital days (-0.80 days, -36.7%), antibiotic days (-1.49 days, -29.5%), and percent 30-day mortality (-1.67%, -13.64%) were driven by HostDx Sepsis providing fewer “noninformative” moderate risk predictions and more “certain” low- or high-risk predictions compared to standard of care, especially for patients who were not severely ill. These results were robust to changes in key parameters, including disease prevalence. Conclusions: Our model shows substantial savings associated with introduction of HostDx Sepsis among patients with ARTIs in EDs. These results need confirmation in interventional trials.

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