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

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

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.

Study Overview

• Status: Completed
• Conditions: Fungal Infection by Site
• Intervention / Treatment: Drug: Fluconazole

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14226
      • CPL Associates,LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 85 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is a multi-center study of adult and pediatric patients hospitalized with severe infection caused by C. albicans. An announcement of this case series collection study will be sent to our ongoing list of primary care practitioners, hospitalists, specialists in infectious diseases, pulmonologists, clinical pharmacists, and other investigators throughout the USA.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fluconazole; 30 evaluable 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.	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

Collaborators and Investigators

• Sponsor: CPL Associates
• Collaborators: Astellas Pharma US, Inc.
• Investigators: Principal Investigator: Jerome Schentag, Pharm.D., CPL Associates, LLC; Principal Investigator: Joseph Paladino, Pharm.D., CPL Associates, LLC

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: July 22, 2008
• First Submitted That Met QC Criteria: July 23, 2008
• First Posted (Estimate): July 24, 2008

Study Record Updates

• Last Update Posted (Estimate): July 23, 2014
• Last Update Submitted That Met QC Criteria: July 21, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: fluconazole; C. albicans
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Mycoses; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: MYCA-8F16