Infection With Unknown Origin in the Emergency Department

A Descriptive Study of Patients Suspected With Infection in the Emergency Department, With a Special Focus on Infection With Unknown Origin.

Patients suspected with infection is one of the major groups, who are admitted to the Danish Emergency Departments (ED). Currently, there is no overall description of the distribution of these infections. The aim of this study is to characterize ED patients with a suspected infection whereby the focus of the infection is of an unknown origin.

Study Overview

• Status: Completed
• Conditions: Infection
• Intervention / Treatment: Diagnostic test: Broader Medical history and clinical tests

Detailed Description

Bacteria resistant to antibiotics are associated with high antibiotic consumption and are identified by the World Health Organisation as a major public health threat. Despite efforts to optimize antibiotic consumption in Denmark, the total consumption in the hospital sector increased from 2009-2018 and the incidence of multi-resistance bacteria (MRB) is increasing. A Danish multicenter study has shown that every 20th patient in the emergency department has MRB. Patients with an infection of unknown origin tend to be prescribed a broad-spectrum antibiotic, as physicians endeavour to target probable origins in the body. The uncertainty associated with the diagnosis may lead to an overconsumption of antibiotics, which contributes to increased development of resistant bacteria and threatens future treatment options.

The aim of this study is to characterize patients admitted to the ED suspected with infection. The study will have three objectives:

• To describe the distribution of ED infections according to the registered diagnosis in the medical record compared to a clinical expert panel assessment
• To identify clinically relevant information available at admission associated with a patients infection of unknown origin.
• To investigate the association between an adverse event and clinically relevant information for patients with infection of unknown origin

The investigators' hypothesis is that with an improvement of knowledge about patients with an infection of unknown origin, a more accurate diagnosis can be made leading to a more appropriate antibiotic therapy and contributing to the fight against resistance to antibiotics.

• 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 suspected with infection at three hospitals in the region of Southern Denmark - Hosptial Sonderjylland, Hospital Lillebaelt and Odense University Hospital.

Description

Inclusion Criteria:

• Adults admitted to the ED will be invited to participate in the study, if the physician, receiving the patient, suspect the patient has an infection (e.g. indication for blood culture).

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?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with a suspected infection; Acutely admitted patients from the emergency department across 3 sites who have a suspected infection.	Diagnostic test: Broader Medical history and clinical tests; Patients will be treated with standard care plus additional blood tests, urine culture and urine flow cytometry,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis after 2 days	Diagnosis code of patient (registered medical record and clinical expert panel assessment)	48 hours after admission emergency department

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-hospital mortality	binary	within 60 days from admission to the emergency department
Intensive care unit treatment	Transfer to the intensive care unit will be recorded during the current hospitalization as a binary variable (transferred/not-transferred)	within 60 days from admission to the emergency department
Length of stay	Defined as the time (in days) spent in hospital during the current admission. Measured in days from admission to hospital discharge. Discharge date minus admission date	within 60 days from admission to the emergency department
30-days mortality	Mortality within 30 days from admission to the Emergency Department	within 30 days from admission to the emergency department
Readmission	Binary	within 30 days from day of discharge
Diagnose code at hospital discharge	code registered in medical record at discharge	within 60 days from admission to the emergency department

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day mortality	Mortality - binary	Within 90 days from admission to emergency department
Level of infection markers	concentration of serum procalcitonin, CRP and suPAR	Within 4 hours of arrival to emergency department
Level of markers of lung injury	concentration of serum surfactant protein D, KL-6, and YKL-40	Within 4 hours of arrival to emergency department
Bacteriuria	defined by microbiologist on urine culture analysis	Within 4 hours of arrival to emergency department

Collaborators and Investigators

• Sponsor: University of Southern Denmark
• Investigators: Study Chair: Christian Backer Mogensen, University Hospital of Southern Denmark

Publications and helpful links

General Publications

• Skjot-Arkil H, Mogensen CB, Lassen AT, Johansen IS, Chen M, Petersen P, Andersen KV, Ellermann-Eriksen S, Moller JM, Ludwig M, Fuglsang-Damgaard D, Nielsen FE, Petersen DB, Jensen US, Rosenvinge FS. Carrier prevalence and risk factors for colonisation of multiresistant bacteria in Danish emergency departments: a cross-sectional survey. BMJ Open. 2019 Jun 27;9(6):e029000. doi: 10.1136/bmjopen-2019-029000.
• 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.
• Carter-Storch R, Olsen UF, Mogensen CB. Admissions to emergency department may be classified into specific complaint categories. Dan Med J. 2014 Mar;61(3):A4802.
• Bager F. DANMAP: monitoring antimicrobial resistance in Denmark. Int J Antimicrob Agents. 2000 May;14(4):271-4. doi: 10.1016/s0924-8579(00)00135-7.
• Zhao MZ, Ruan QR, Xing MY, Wei S, Xu D, Wu ZH, Zhu L, Zhu JL, Zheng CF, Liu S, Yu ZJ, Qi JY, Song JX. A Diagnostic Tool for Identification of Etiologies of Fever of Unknown Origin in Adult Patients. Curr Med Sci. 2019 Aug;39(4):589-596. doi: 10.1007/s11596-019-2078-3. Epub 2019 Jul 25.
• Courjon J, Demonchy E, Degand N, Risso K, Ruimy R, Roger PM. Patients with community-acquired bacteremia of unknown origin: clinical characteristics and usefulness of microbiological results for therapeutic issues: a single-center cohort study. Ann Clin Microbiol Antimicrob. 2017 May 19;16(1):40. doi: 10.1186/s12941-017-0214-0.

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 8, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 9, 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: fever; diagnosis; antibiotics; pyrexia; source
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Emergencies; Infections; Communicable Diseases
• Other Study ID Numbers: SHS-ED-11f-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