Invasive Candidiasis in Critical Care

The combination of acute phase marker monitoring and the "T2Candida" assay (name of the test) will represent an acceleration of the identification of the causative agent of mycotic infection, a significant improvement in the specificity and positive predictive value of this strategy in the diagnosis of invasive candidiasis and candidemia in ICU patients, thereby improving the clinical condition of patients and reducing the cost of specific antifungal therapy.

Study Overview

• Status: Recruiting
• Conditions: Invasive Candidiasis
• Intervention / Treatment: Diagnostic test: Invasive candidiasis test; Other: Urine sample collection for future research

Detailed Description

Speed of response in the treatment of sepsis is crucial for the patient. The time from the collection of a positive haemoculture to the identification of the causative agent of sepsis is around 2 days; therefore, physicians in intensive care units deploy combined empiric antibiotic and antifungal therapy immediately when acute phase markers such as procalcitonin, interleukin-6, Presepsin, C-reactive protein are elevated. A new acute phase marker is lipopolysaccharide-binding protein, which, together with Presepsin, appears to be a suitable marker to distinguish invasive candida infections from bacterial infections. But its kinetics needs to be further analyzed.

At the same time, the causative agent of sepsis, G-/G+ bacteria or yeast, must be identified as soon as possible. Haemoculture and culture of the established drain is the gold standard, but the disadvantage is the low sensitivity and the time delay to obtain the result. It is therefore advisable to combine haemoculture with molecular biology-based tests that can identify the causative organism within hours. Conversely, the disadvantage of these tests is that they identify only the most common sepsis pathogens and do not determine susceptibility to antibiotics and antifungals, but the advantage is that with prophylaxis in place, these tests are often positive when haemoculture is negative. The T2Candida test can detect Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei and Candida parapsilosis, which are the more common causative agents of mycotic bloodstream infections.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Jiří Hynčica; Phone Number: 2587 0042059737; Email: jiri.hyncica@fno.cz

Study Locations

• Czechia
  • Prague, Czechia, 150 06
    • Recruiting
    • University Hospital Motol
    • Contact: Vanda Chrenková, MD; Phone Number: 5390 0042022443; Email: vanda.chrenkova@fnmotol.cz
    • Principal Investigator: Vanda Chrenková, MD
  • Moravian-Silesian Region
    • Ostrava, Moravian-Silesian Region, Czechia, 708 52
      • Recruiting
      • University Hospital Ostrava
      • Contact: Jiří Hynčica; Phone Number: 2587 0042059737; Email: jiri.hyncica@fno.cz
      • Principal Investigator: Hana Slepčanová, Mgr.
      • Sub-Investigator: Marcela Káňová, Assoc.Prof.,MD,PhD
      • Sub-Investigator: Tomáš Zaoral, MD,PhD
      • Sub-Investigator: Radim Dobiáš, Mgr.,PhD
      • Sub-Investigator: Iveta Láryšová

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with suspected invasive candidasis.

Description

Inclusion Criteria:

• critically ill patients
• new onset sepsis
• rise in body temperature >38°C according to The Third Consensus Definitions for Sepsis and Septic Shock
• colonization with Candida spp. from more than 1 non-sterile site
• body temperature >38 °C despite 5 days of broad-spectrum antibiotic therapy with the presence of at least 1 of the following risk factors: abdominal surgery, secondary peritonitis, pancreatitis, central venous catheter (CVC) insertion, total parenteral nutrition (CPV), dialysis, steroid therapy, immunosuppressive therapy, or liver transplantation
• microbiological test results will be reviewed and categorized based on whether Candida sp. is isolated from at least 2 non-sterile sites (±3 days) and whether there is an alternative microbiological diagnosis.

Exclusion Criteria:

• not signing the informed consent with participation in the study
• administration of antifungal therapy prior to collection of the biological material required for the study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with suspected invasive candidiasis; Patients with suspected invasive candidiasis will be enrolled in this study arm.	Diagnostic test: Invasive candidiasis test; The combination of acute phase marker monitoring and the T2Candida assay will be assessed.; Other: Urine sample collection for future research; Patients will be asked to provide a urine sample for future research (urine biobank).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute-phase biomarkers dynamics - procalcitonin	The levels of procalcitonin will be observed in time and measured in μg/L. The follow-up will last 8 days, the patient may be observed repeatedly, depend-ing on the patient's condition.	8 days
Acute-phase biomarkers dynamics - interleukin-6	The levels of interleukin-6 will be observed in time and measured in pg/ml. The follow-up will last 8 days, the patient may be observed repeatedly, depend-ing on the patient's condition.	8 days
Acute-phase biomarkers dynamics - interleukin-10	The levels of interleukin-10 will be observed in time and measured in pg/ml. The follow-up will last 8 days, the patient may be observed repeatedly, depend-ing on the patient's condition.	8 days
Acute-phase biomarkers dynamics - Presepsin	The levels of Presepsin will be observed in time and measured in pg/ml. The follow-up will last 8 days, the patient may be observed repeatedly, depend-ing on the patient's condition.	8 days
Acute-phase biomarkers dynamics - C-reactive protein	The levels of C-reactive protein will be observed in time and measured in mg/dL. The follow-up will last 8 days, the patient may be observed repeatedly, depend-ing on the patient's condition.	8 days
Acute-phase biomarkers dynamics - 1,3-β-D-glucan	The levels of C-reactive protein will be observed in time and measured in pg/ml. The follow-up will last 8 days, the patient may be observed repeatedly, depend-ing on the patient's condition.	8 days
Acute-phase biomarkers dynamics - pentraxin 3	The levels of C-reactive protein will be observed in time and measured in ng/ml. The follow-up will last 8 days, the patient may be observed repeatedly, depend-ing on the patient's condition.	8 days
T2Candida test	The T2Candida test is able to detect the presence of Candida albicans, C. tropicalis, C. glabrata, C. krusei and C. parapsilosis. The results will be assessed as positive or negative.	One-time measurement at the enrolment into the study
Lipopolysaccharide binding protein	The levels of Lipopolysaccharide binding protein (LBP)_S/P will be observed in time and measured in mg/L. The follow-up will last 8 days, the patient may be observed repeatedly, depend-ing on the patient's condition.	One-time measurement at the enrolment into the study

Collaborators and Investigators

• Sponsor: University Hospital Ostrava
• Collaborators: University Hospital, Motol
• Investigators: Principal Investigator: Hana Slepčanová, Mgr., University Hospital Ostrava

Publications and helpful links

General Publications

• Dobias R, Kanova M, Petejova N, Pisti SK, Bocek R, Krejci E, Struzkova H, Cachova M, Tomaskova H, Hamal P, Havlicek V, Raska M. Combined Use of Presepsin and (1,3)-beta-D-glucan as Biomarkers for Diagnosing Candida Sepsis and Monitoring the Effectiveness of Treatment in Critically Ill Patients. J Fungi (Basel). 2022 Mar 17;8(3):308. doi: 10.3390/jof8030308.
• Bassetti M, Giacobbe DR, Vena A, Wolff M. Diagnosis and Treatment of Candidemia in the Intensive Care Unit. Semin Respir Crit Care Med. 2019 Aug;40(4):524-539. doi: 10.1055/s-0039-1693704. Epub 2019 Oct 4.

Helpful Links

• World Health Organisation (WHO) fungal priority pathogens list to guide research, development and public health action

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 4, 2024
• First Submitted That Met QC Criteria: June 12, 2024
• First Posted (Actual): June 13, 2024

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: June 2, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: biomarkers; invasive candidiasis; candida sepsis
• Additional Relevant MeSH Terms: Invasive Fungal Infections; Infections; Bacterial Infections and Mycoses; Mycoses; Candidiasis; Candidiasis, Invasive
• Other Study ID Numbers: ULM-01-Invasive candidiasis; 03/RVO-FNOs/2024 (Other Grant/Funding Number: University Hospital Ostrava); SGS06/LF/2024 (Other Grant/Funding Number: Faculty of Medicine, University of Ostrava)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make individual participant data available to other researchers. The data may be provided upon request.

Drug and device information, study documents

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