Candida Spp. in the Lower Respiratory Tract: Harmless Residents or Pathogen?

April 2, 2015 updated by: Robert Krause, MD
In critically ill patients Candida spp. are frequently isolated from respiratory tract secretions such as endotracheal aspirates and bronchoalveolar lavages (BAL) and are most often considered as colonizers of the respiratory tract. In contrast, pneumonia due to infection with Candida spp. is rare and is diagnosed by histological demonstration of the yeast in lung tissue with associated inflammation. In spite of this, preemptive antifungal therapy based on isolation of Candida spp. from the respiratory tract is often initiated in critically ill patients. The disadvantages of this approach include increased selective pressure for the development of antimicrobial resistance, potential risks of adverse drug reactions and high treatment costs. On the other hand, immediate administration of appropriate antifungal therapy has been shown to be an important predictor of favorable outcome for patients with invasive fungal infections. Therefore, the development of reliable diagnostic measures for the detection of invasive pulmonary candidiasis is crucial. The overall objective of the proposed research project is to identify diagnostic strategies to differentiate between Candida colonization and Candida infection of the lower respiratory tract in critically ill patients. The proposed projects intends to test the hypothesis that 1.) invasive Candida strains from the lower respiratory tract differ from colonizing Candida strains with regard to production and expression of putative virulence factors and/or that 2.) patients suffering from pulmonary invasive candidiasis differ from patients colonized by Candida spp. with regard to inflammatory markers, other serum markers (fungal antigen) and composition of indigenous pulmonary bacterial flora.

Study Overview

Status

Completed

Conditions

Detailed Description

In critically ill patients Candida spp. are frequently isolated from respiratory tract secretions such as endotracheal aspirates and bronchoalveolar lavages (BAL) and are most often considered as colonizers of the respiratory tract. In contrast, pneumonia due to infection with Candida spp. is rare and is diagnosed by histological demonstration of the yeast in lung tissue with associated inflammation. In spite of this, preemptive antifungal therapy based on isolation of Candida spp. from the respiratory tract is often initiated in critically ill patients. The disadvantages of this approach include increased selective pressure for the development of antimicrobial resistance, potential risks of adverse drug reactions and high treatment costs. On the other hand, immediate administration of appropriate antifungal therapy has been shown to be an important predictor of favorable outcome for patients with invasive fungal infections. Therefore, the development of reliable diagnostic measures for the detection of invasive pulmonary candidiasis is crucial. The overall objective of the proposed research project is to identify diagnostic strategies to differentiate between Candida colonization and Candida infection of the lower respiratory tract in critically ill patients. The proposed projects intends to test the hypothesis that 1.) invasive Candida strains from the lower respiratory tract differ from colonizing Candida strains with regard to production and expression of putative virulence factors and/or that 2.) patients suffering from pulmonary invasive candidiasis differ from patients colonized by Candida spp. with regard to inflammatory markers, other serum markers (fungal antigen) and composition of indigenous pulmonary bacterial flora. For this purpose, pathogen related factors such as Candida prevalence, Candida quantity, phospholipases, secreted aspartyl proteinases, chromosome length polymorphism, transcriptional profiles, DFG16, SAP1-3, and SAP5 mRNA as well as human cellular and serum markers such as Dectin-1, TLR-2, TLR-4, TNF-α, IL-2, IL-10, IL-12, procalcitonin and (1→3) ß-D-Glucan, the indigenous pulmonary bacterial flora and underlying risk factors will be investigated in 6 different patient groups in this project. The results of this study should contribute to a better understanding of Candida colonization and Candida infections in the lower respiratory tract in critically ill patients. This should prospectively lead to a more targeted antifungal therapy and to a better outcome as well as to a reduction of unnecessary antifungal treatments and to a reduction of treatment costs in the future.

Study Type

Observational

Enrollment (Actual)

202

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
    • Styria
      • Graz, Styria, Austria, 8043
        • Medical University of Graz

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

adult patients with and without infiltration of the lungs and with and without intubation and mechanically ventilation

Description

Inclusion Criteria:

  • depending on study group; i.e. no pathology of the lungs in group 1, and 4; underlying disease of the lungs in group 2 (i.e. sarcoidosis etc), infiltration of the lungs in group 3,4,5

Exclusion Criteria:

  • depending on study group: i.e. HIV, recent antifungal therapy, age below 18

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
pathogenic relevance of Candida in lower respiratory tract
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Robert Krause, MD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (ACTUAL)

April 1, 2015

Study Completion (ACTUAL)

April 1, 2015

Study Registration Dates

First Submitted

November 5, 2008

First Submitted That Met QC Criteria

November 5, 2008

First Posted (ESTIMATE)

November 6, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

April 3, 2015

Last Update Submitted That Met QC Criteria

April 2, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19-322 ex 07/08

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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