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Enteral fluconazole is well absorbed in critically ill surgical patients
Robert K Pelz1, Pamela A Lipsett, Sandra M Swoboda
1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background:
Enteral fluconazole, a triazole antifungal agent with an excellent oral bioavailability, has not been widely studied in critically ill surgical patients.
Methods:
During a randomized placebo-controlled trial of enteral fluconazole (N = 130) versus placebo (N = 130) for the prevention of fungal infections in critically ill surgical patients, trough fluconazole levels were measured after the loading dose and 3 times weekly during intensive care unit stay. Minimum inhibitory concentrations (MICs) for fluconazole were measured on all infecting Candida isolates.
Results:
Four hundred sixty-seven serum samples were assayed for fluconazole levels in 121 patients. The most common infecting fungal species was Candida albicans, isolated in 14 of 31 infections (45%). Other infecting species were C glabrata, C tropicalis, and C parapsilosis. Mean fluconazole levels were above the highest MIC for C albicans and C parapsilosis in all but 5 patients (4%). Mean fluconazole levels were below the median MIC for C glabrata in 93 of 121 patients (77%). No significant relationship was seen between fluconazole levels and risk for fungal infection.
Conclusions:
Serum fluconazole levels are above the MIC of most yeast species found in these patients. These levels may not be above the MIC of C glabrata, the second most common Candida isolate causing infection in this study.
Insights
Enteral fluconazole levels in critically ill surgical patients were generally effective against common Candida species. However, levels were often insufficient for Candida glabrata, a frequent cause of infection.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Enteral fluconazole, a triazole antifungal, has limited study in critically ill surgical patients.
- Assessing antifungal efficacy in this population is crucial for patient outcomes.
Purpose of the Study:
- To evaluate serum fluconazole levels and their relationship to minimum inhibitory concentrations (MICs) in critically ill surgical patients.
- To determine the effectiveness of enteral fluconazole in preventing fungal infections in this cohort.
Main Methods:
- A randomized placebo-controlled trial involving 260 critically ill surgical patients (130 fluconazole, 130 placebo).
- Trough fluconazole levels were measured post-loading dose and weekly.
- MICs for fluconazole were determined for all infecting Candida isolates.
Main Results:
- Serum fluconazole levels were assessed in 121 patients, with Candida albicans being the most common isolate.
- Mean fluconazole levels exceeded MICs for Candida albicans and Candida parapsilosis in most patients.
- However, levels were below the median MIC for Candida glabrata in 77% of patients.
Conclusions:
- Serum fluconazole levels achieved in critically ill surgical patients are adequate for most common yeast species.
- Fluconazole levels may be suboptimal for treating infections caused by Candida glabrata, necessitating further investigation.