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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Robert Krause, MD, Medical University of Graz
ClinicalTrials.gov Identifier:
NCT00786903
First received: November 5, 2008
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

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.


Condition
Pulmonary Candidiasis
Invasive Candidiasis

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Candida Spp. in the Lower Respiratory Tract: Harmless Residents or Pathogen?

Resource links provided by NLM:


Further study details as provided by Medical University of Graz:

Primary Outcome Measures:
  • pathogenic relevance of Candida in lower respiratory tract [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Respiratory secretions, blood, lung tissue


Estimated Enrollment: 350
Study Start Date: November 2008
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00786903

Locations
Austria
Medical University of Graz
Graz, Styria, Austria, 8043
Sponsors and Collaborators
Robert Krause, MD
Investigators
Principal Investigator: Robert Krause, MD Medical University of Graz
  More Information

No publications provided by Medical University of Graz

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Robert Krause, MD, Assistent Head of the Pulmonology Department, Medical University of Graz
ClinicalTrials.gov Identifier: NCT00786903     History of Changes
Other Study ID Numbers: 19-322 ex 07/08
Study First Received: November 5, 2008
Last Updated: February 6, 2014
Health Authority: Austria: Agency for Health and Food Safety

Additional relevant MeSH terms:
Candidiasis
Candidiasis, Invasive
Mycoses

ClinicalTrials.gov processed this record on October 23, 2014