Diagnostic Accuracy of Urine Flow Cytometry in Excluding Bacteruria

Diagnostic Accuracy of Urine Flow Cytometry in Diagnosing and Excluding Bacteruria in the Emergency Department

A more rapid test for bacteriuria is desired. This will exclude the patients not having bacteriuria, which will contribute to a more rapid and accurate diagnosis of infectious diseases. The aim of the study is to investigate the diagnostic accuracy of point-of-care urine flow cytometry on diagnosing and excluding bacteriuria

Study Overview

• Status: Completed
• Conditions: Acute Infection
• Intervention / Treatment: Diagnostic test: urine flow cytometry

Detailed Description

A prerequisite for the appropriate use of antibiotics is timely access to accurate diagnostic tests, since treatment of acute infections should be initiated within a few hours to avoid serious complications such as bacteremia, sepsis, organ failure, septic shock and death.

The diagnosis of urinary tract infections including acute pyelonephritis (APN) is difficult due to often weak and non-specific symptoms and high incidence of asymptomatic bacteruria in especially elderly patients. The diagnosis is verified by significant bacteriuria in urine culture.

Unfortunately, the time from urine sample to result from urine cultures is more than 24 hours days. Urine test strips are unreliable with low specificity and low predictive values. Therefore, a point-of-care (POC) test is desired, which can provide rapid results and quickly identify a bacteriuria. One such tool may be urine flow cytometry (UFC), which has shown promising diagnostic value for the exclusion of bacteriuria with a high negative predictive value. However, better documentation for its use as an ED diagnostic screening method is needed.

The aim of the study is to investigate the diagnostic accuracy of POC-UFC on diagnosing and excluding bacteriuria? Our hypothesis is that by excluding patients not having bacteriuria, it will contribute to a more rapid and accurate diagnosis

• Study Type: Observational
• Enrollment (Actual): 966

Contacts and Locations

Study Locations

• Denmark
  • Aabenraa, Denmark
    • Hospital of Southern Jutland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Acutely admitted patients with suspected infections from three emergency departments (EDs) in the Region of Southern Denmark (Hospital Sønderjylland, Hospital Lillebælt, Odense University Hospital)

Description

Inclusion Criteria:

• Suspicion of acute infections assessed by the receiving physician at the emergency department

Exclusion Criteria:

• If the attending physician considers that participation will delay a life-saving treatment or patient needs direct transfer to the intensive care unit.
• Admission within the last 14 days
• Verified COVID-19 disease within 14 days before admission
• Pregnant women
• Severe immunodeficiencies: Primary immunodeficiencies and secondary immunodeficiencies (HIV positive CD4 <200, Patients receiving immunosuppressive treatment (ATC L04A), Corticosteroid treatment (>20 mg/day prednisone or equivalent for >14 days within the last 30 days), Chemotherapy within 30 days)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Suspected infection; All patients admitted to the emergency department with suspected infections assessed by the receiving physician

Diagnostic test: urine flow cytometry; Diagnostic test of urine flow cytometry. A urine sample will be collected according to routine procedure by a study assistant. The sample will be divided into two aliquots; half for routine urine culturing, and half for Point-of-care Urine Flow cytometry (POC-UFC) analysis (UF-5000, Sysmex, Kobe, Japan). The analysis will be performed according to manufacturer's instruction and conducted by laboratory staff. Laboratory staff will be blinded to the participants diagnosis and outcome. The results of the POC-UFC analysis will not be visible to the treating physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacteriuria	The urine culture analysis combined with microbiologist assessment will be used as reference standard for bacteriuria. Diagnostic accuracy will be conducted, and Youden index analysis will be used to estimate the best cut-off	urine collected within 4 hours of arrival to emergency department and analysed within one week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verified infectious diagnosis by expert panel	An expert panel will define the final diagnosis (including APN) based on all findings during admission. The expert panel consists of two independent consultants from the emergency department with significant experience in emergency medicine and acute infections. They will individually determine the type of infection the patient admitted actually had. The final diagnosis will be based on all available relevant information from the patient medical record including MRI of kidneys and HR-CT of lungs. A standardized template will be used. Disagreement will be discussed until a consensus is reached.	2 months after discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensive care unit treatment	transfer to ICU during current admission (binary outcome)	within 60 days from admission to emergency department
Length of stay	days spent in hospital during current admission	within 60 days from admission to emergency department
The number of participants who died within 30 days	binary - 30-days mortality	within 30 days from arrival day
The number of participants who died within 90 days	binary - 90 days mortality	within 90 days from arrival day
Readmission	binary	within 30 days from day of discharge
In-hospital mortality	binary	within 60 days from admission to emergency department
Level of infection markers	Concentration of serum procalcitonin, CRP and suPAR	blood collected within 4 hours of arrival to emergency department
Urological intervention	Number of patients, who during the course of admission with suspected acute pyelonephritis requires urological interventions	Measured 7 days after admission

Collaborators and Investigators

• Sponsor: University of Southern Denmark

Publications and helpful links

General Publications

• Skjot-Arkil H, Heltborg A, Lorentzen MH, Cartuliares MB, Hertz MA, Graumann O, Rosenvinge FS, Petersen ERB, Ostergaard C, Laursen CB, Skovsted TA, Posth S, Chen M, Mogensen CB. Improved diagnostics of infectious diseases in emergency departments: a protocol of a multifaceted multicentre diagnostic study. BMJ Open. 2021 Sep 30;11(9):e049606. doi: 10.1136/bmjopen-2021-049606.
• Koves B, Cai T, Veeratterapillay R, Pickard R, Seisen T, Lam TB, Yuan CY, Bruyere F, Wagenlehner F, Bartoletti R, Geerlings SE, Pilatz A, Pradere B, Hofmann F, Bonkat G, Wullt B. Benefits and Harms of Treatment of Asymptomatic Bacteriuria: A Systematic Review and Meta-analysis by the European Association of Urology Urological Infection Guidelines Panel. Eur Urol. 2017 Dec;72(6):865-868. doi: 10.1016/j.eururo.2017.07.014. Epub 2017 Jul 25.
• Herraez O, Asencio MA, Carranza R, Jarabo MM, Huertas M, Redondo O, Arias-Arias A, Jimenez-Alvarez S, Solis S, Zamarron P, Illescas MS, Galan MA. Sysmex UF-1000i flow cytometer to screen urinary tract infections: the URISCAM multicentre study. Lett Appl Microbiol. 2018 Mar;66(3):175-181. doi: 10.1111/lam.12832. Epub 2018 Jan 28.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): February 28, 2022
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: December 22, 2020
• First Submitted That Met QC Criteria: December 22, 2020
• First Posted (Actual): December 28, 2020

Study Record Updates

• Last Update Posted (Actual): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: diagnosis; urinary tract infections; Emergency department; Acute infections; bacteruria
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: SHS-ED-12b-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No