Outcomes of Patients Who Fail to Respond to Fluconazole Treatment of Severe Candida Albicans Infections

Fungal Infection by Site Clinical Trial

Official title:

A Case Series of Investigator-Identified Fluconazole Failures: Outcome Characterization of Patients Who Fail to Respond to Fluconazole Treatment of Severe Infections Caused by Candida Albicans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00721487
• Other study ID #: MYCA-8F16
• Status: Completed
• Phase: N/A
• First received: July 22, 2008
• Last updated: July 21, 2014
• Start date: July 2008
• Est. completion date: December 2009

Study information

• Verified date: July 2014
• Source: CPL Associates
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The primary aims of this study are to identify and characterize the immediate consequences of patients who fail fluconazole treatment during the treatment of severe infection, and to determine if fluconazole failures are more frequently associated with fluconazole-resistant or fluconazole-susceptible strains of C. albicans.

Description:

The primary aims of this study are to identify and characterize the immediate consequences of patients who fail fluconazole treatment during the treatment of severe infection, and to determine if fluconazole failures are more frequently associated with fluconazole-resistant or fluconazole-susceptible strains of C. albicans (i.e. does in vitro resistance matter?). Perhaps the breakpoints are not correct and need to be changed, as has recently happened with vancomycin.

A third objective is to calculate fluconazole PK/PD parameters such as AUIC, and compare the calculated AUIC values of patients who fail with fluconazole-susceptible vs fluconazole-resistant isolates. Specifically for fluconazole, the question here is whether dose matters, and can aggressive dosing offset higher MICs. Thus in all cases, we will also determine the AUIC of fluconazole in order to fully characterize the impact of dose chosen on the outcomes of treated patients who fail to respond to fluconazole. The clinical, microbiological, and pharmacoeconomic outcomes of patients who fail fluconazole therapy and are subsequently hospitalized with severe infections caused by C. albicans will be documented and described.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Medical history, clinical signs and symptoms, and radiological findings consistent with severe C. albicans infection. For example, the criteria for pneumonia are as follows:

1. A core body temperature >38C [100.4F] or <36.1 C [97oF] or leukocytosis (blood leukocyte count >10,000 cells/mm3) or bandemia (>10% bands).

2. Chest radiographic examination that shows a new or progressive infiltrate, consolidation, cavitation, or pleural effusion.

3. Rales, dullness to percussion, or decreased breath sounds on physical examination of the chest, new onset of purulent sputum, or change in character of sputum.

2. A positive culture must demonstrate the presence of C. albicans, isolated from a properly obtained respiratory or blood sample, collected within 72 hours of admission to a hospital. All patients with respiratory cultures must produce sputum with Gram stain analysis indicating the relative absence of contaminating oropharyngeal squamous cells and the presence of a significant number of WBCs and morphologically distinct bacteria. Fluconazole sensitivity testing results must be available for the initial C. albicans isolate.

3. Must have received, and failed to respond to, at least 4 days of treatment with fluconazole.

4. Admitted to a hospital or ICU for treatment of a severe infection.

Exclusion Criteria:

1. Pregnant or lactating women

2. Cystic fibrosis

3. Life expectancy <3 months from underlying disease

4. Underlying lung carcinoma

Study Design

Observational Model: Case-Only, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Fungal Infection by Site
• Infection
• Mycoses

Intervention

Drug:
• Fluconazole
Patients hospitalized with severe infection caused by C. albicans, documented by standard clinical signs, symptoms, and radiology, and having failed at least four days of fluconazole therapy

Locations

Country	Name	City	State
United States	CPL Associates,LLC	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
CPL Associates	Astellas Pharma US, Inc.

Country where clinical trial is conducted

United States,