Non-Conventional Microbiological Methods in the Diagnosis of Candidemia

The Importance of Non-Conventional Microbiological Methods in the Diagnosis of Candidemia and the Host Cytokine Response to Different Fungal Pathogens

This study evaluates the diagnostic value of non-conventional microbiological methods for early detection of candidemia and invasive candidiasis in adult hospitalized patients with suspected invasive fungal infection. Conventional blood culture remains the gold standard for diagnosis but has limited sensitivity and may delay initiation of targeted antifungal therapy.

The study investigates whether the combined use of serum biomarkers (1,3)-β-D-glucan, mannan and anti-mannan antibodies, and molecular detection of Candida DNA by PCR improves the diagnostic performance compared with conventional culture-based methods.

In addition, the study explores the host cytokine response associated with different Candida species and other fungal pathogens. The goal is to support the development of an optimized diagnostic algorithm for invasive fungal disease and improve clinical management of critically ill patients.

Study Overview

• Status: Completed
• Conditions: Candidemia; Invasive Candidiasis
• Intervention / Treatment: Diagnostic test: Candida Diagnostic Testing Panel

Detailed Description

Early diagnosis of invasive fungal infections, particularly candidemia and invasive candidiasis, is essential for timely initiation of appropriate antifungal therapy and improvement of patient outcomes. Despite being considered the current diagnostic gold standard, blood culture has limited sensitivity and may remain negative in a substantial proportion of patients with invasive candidiasis. In addition, culture-based identification of fungal pathogens is time-consuming and may delay targeted treatment decisions.

To address these limitations, alternative diagnostic approaches have been developed, including detection of fungal cell wall biomarkers and molecular assays. Serum biomarkers such as (1,3)-β-D-glucan, mannan antigen, and anti-mannan antibodies may provide earlier indication of invasive Candida infection compared with blood culture. Molecular detection of Candida DNA by polymerase chain reaction (PCR) may also offer higher sensitivity and faster turnaround time.

This interventional diagnostic study evaluates the clinical and diagnostic utility of a combined non-conventional microbiological testing panel in adult patients with clinical suspicion of invasive/systemic fungal infection and risk factors for invasive fungal disease (e.g., ICU admission, central venous catheters, broad-spectrum antibiotics, parenteral nutrition, corticosteroid therapy, chemotherapy, immunosuppression, neutropenia, hemodialysis, mechanical ventilation, and Candida colonization).

Participants undergo routine blood culture testing for bacteria and fungi as part of standard clinical care. In addition, blood samples are collected for the following diagnostic tests:

Serum (1,3)-β-D-glucan

Mannan antigen and anti-mannan antibodies

PCR-based detection of Candida DNA from EDTA whole blood

Samples are processed according to routine laboratory procedures in participating microbiology laboratories. Blood culture-positive Candida isolates are identified and stored for further analyses. Participants are categorized into study groups based on blood culture results (Candida-positive blood culture group, bacterial-positive blood culture group, and blood culture-negative group). A healthy volunteer control group may be included for comparative purposes.

The primary objective is to determine whether the combined non-conventional diagnostic panel improves detection of candidemia/invasive candidiasis compared with conventional blood culture alone. Secondary objectives include evaluation of the diagnostic performance of individual biomarkers and PCR testing, assessment of the time to diagnosis, and analysis of host cytokine response patterns associated with different fungal pathogens.

The overall aim of the study is to support the development of an optimized diagnostic algorithm for invasive fungal disease, improve early detection, and reduce unnecessary or delayed antifungal treatment in critically ill patients.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Institute of Oncology Ljubljana

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult hospitalized patients (≥18 years)
• Clinical suspicion of invasive/systemic fungal infection (suspected fungal sepsis)
• Presence of risk factors for invasive fungal disease (e.g., ICU admission, central/peripheral venous catheters, parenteral nutrition, broad-spectrum antibiotic therapy >3 days, corticosteroid therapy, chemotherapy, immunosuppression, neutropenia, hemodialysis, mechanical ventilation, or Candida colonization)

Exclusion Criteria:

• Age <18 years
• Insufficient blood sample for additional diagnostic testing
• Refusal or inability to provide informed consent (if applicable)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Non-Conventional Diagnostic Testing Panel; Adult hospitalized patients with suspected invasive fungal infection underwent routine blood culture testing and additional non-conventional diagnostic testing including serum (1,3)-β-D-glucan, mannan/anti-mannan antibodies, and PCR-based detection of Candida DNA in blood samples, in order to evaluate the diagnostic utility of combined microbiological methods for early detection of candidemia.

Diagnostic test: Candida Diagnostic Testing Panel; Participants underwent routine blood culture testing for bacteria and fungi and additional non-conventional diagnostic testing for suspected invasive candidiasis, including serum (1,3)-beta-D-glucan, mannan antigen, anti-mannan antibodies, and PCR-based detection of Candida DNA from EDTA whole blood samples. The combined diagnostic panel was used to assess its potential value for earlier and improved detection of candidemia compared with conventional culture-based methods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance of the combined non-conventional testing panel for candidemia	Sensitivity and specificity of the combined diagnostic panel (blood culture, Candida PCR, (1,3)-beta-D-glucan, mannan and anti-mannan antibodies) for detection of candidemia and invasive candidiasis in adult hospitalized patients with suspected invasive fungal infection.	At time of diagnostic work-up (baseline)
Diagnostic performance of the combined non-conventional testing panel for candidemia	Sensitivity and specificity of the combined diagnostic panel (blood culture, Candida PCR, (1,3)-beta-D-glucan, mannan and anti-mannan antibodies) for detection of candidemia and invasive candidiasis in adult hospitalized patients with suspected invasive fungal infection.	At time of diagnostic work-up during patient hospitalization

Collaborators and Investigators

• Sponsor: Institute of Oncology Ljubljana

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Candida spp.
• Additional Relevant MeSH Terms: Invasive Fungal Infections; Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Mycoses; Candidiasis; Fungemia; Pathological Conditions, Signs and Symptoms; Candidemia; Candidiasis, Invasive
• Other Study ID Numbers: OI-CAND-DIAG-2015-01; KME_78_06_14 (Other Identifier: National Medical Ethics Committee of the Republic of Slovenia)

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