Empirical anti-Candida therapy among selected patients in the intensive care unit: A cost-effectiveness analysis

Background: Mortality from invasive candidiasis is high. Low culture sensitivity and treatment delay contribute to increased mortality, but nonselective early therapy may result in excess costs and drug resistance. Objective: To determine the cost-effectiveness of anti-Candida strategies for high-risk patients in the intensive care unit (ICU). Design: Cost-effectiveness decision model. Data Sources: Published data to 10 May 2005, identified from MEDLINE and Cochrane Library searches, ICU databases, expert estimates, and actual hospital costs. Target Population: Patients in the ICU with suspected infection who have not responded to antibacterial therapy. Time Horizon: Lifetime. Perspective: Societal. Interventions: Fluconazole, caspofungin, amphotericin B, or lipid formulation of amphotericin B given as either empirical or culture-based therapy and no anti-Candida therapy. Outcome Measures: Incremental life expectancy and incremental cost per discounted life-year (DLY) saved. Results of Base-Case Analysis: Ten percent of the target population will have Invasive candidiasis. Empirical caspofungin therapy is the most effective strategy but is expensive ($295 115 per DLY saved). Empirical fluconazole therapy is the most reasonable strategy ($12 593 per DLY saved) and decreases mortality from 44.0% to 30.4% in patients with invasive candidiasis and from 22.4% to 21.0% in the overall target cohort Results of Sensitivity Analysis: Empirical fluconazole therapy is reasonable for likelihoods of invasive candidiasis greater than 2.5% or fluconazole resistance less than 24.0%. For higher resistance levels, empirical caspofungin therapy is preferred. For low prevalences of invasive candidiasis, culture-based fluconazole is reasonable. For prevalences exceeding 60%, empirical caspofungin therapy is reasonable. For caspofungin to be reasonable at a prevalence of 10%, its cost must be reduced by 58%. Limitations: Less severe illness and limited use of broad-spectrum antimicrobial agents, typical of smaller hospitals, could result in a lower risk for invasive candidiasis. Conclusions: In patients in the ICU with suspected infection who have not responded to antibiotic treatment, empirical fluconazole should reduce mortality at an acceptable cost. The use of empirical strategies in low-risk patients is not justified.