High- versus low-dose fluconazole therapy for empiric treatment of suspected invasive candidiasis among high-risk patients in the intensive care unit: a cost-effectiveness analysis

Abstract

Background: High-dose fluconazole is an alternative for patients with candidemia caused by Candida glabrata or other Candida species with decreased fluconazole susceptibility. However, empiric high-dose fluconazole is not currently recommended and may result in higher drug costs and toxicity. Objective: To determine the cost-effectiveness of using empiric high-dose fluconazole in intensive care unit (ICU) with suspected invasive candidiasis. Design: Decision analytic model. Target population: ICU patients with suspected invasive candidiasis. Time horizon: Lifetime. Perspective: Societal. Interventions: Low-dose fluconazole (loading dose of 800 mg followed by 400 mg daily) vs. high-dose fluconazole (loading dose of 1600 mg followed by 800 mg daily). Generic fluconazole costs were used for the analysis. Outcome measures: Incremental life expectancy and incremental cost per discounted life year (DLY) saved. Result of base-case analysis: Based on current national levels of fluconazole resistance and ability to correctly identify patients with candidemia, high-dose fluconazole was the more effective but more expensive treatment strategy. Empiric high-dose fluconazole therapy decreased the mortality rate by 0.15% compared to low-dose strategy with a cost-effectiveness rate of $55 526 per DLY saved. Results of sensitivity analysis: Empirical high-dose fluconazole was an acceptable treatment strategy (using $100 000 per DLY saved as threshold) unless the physical age of an ICU survivor was 66 years or older. Empirical high-dose fluconazole was an acceptable treatment strategy using $50 000 per DLY saved with minor changes in parameters estimates. Limitations: The estimates of our model may not be applicable to all ICU patients. Other hospitals with differences in fluconazole resistance, prevalence of invasive candidiasis, or duration of fluconazole therapy may produce different results. Conclusion: These results suggest that empiric high-dose fluconazole therapy should reduce the mortality associated with invasive candidiasis at an acceptable cost.