A retrospective Evaluation of fluconazole for the treatment of Candida glabrata fungemia

Abstract

Candida glabrata accounts for 21% of Candida bloodstream isolates in the United States and ranges from susceptible-dose-dependent to resistant to fluconazole. A fluconazole dose of 800 mg/d ( approximately 12 mg/kg per day) is predicted to produce peak plasma concentrations that surpass the susceptible-dose-dependent MIC breakpoint of 16 to 32 mug/mL. Accordingly, the Infectious Diseases Society of America treatment guidelines for candidiasis recommend fluconazole 12 mg/kg per day as an alternative option for treatment of C glabrata fungemia. The main objective of this study was to evaluate fluconazole retrospectively as a treatment for C glabrata fungemia. Data were collected through a database that stores patient information electronically and can be accessed and queried, and chart review at Barnes-Jewish Hospital (St. Louis, Missouri) from January 1999 to August 2002. Eligible patients who had at least 1 positive blood culture for C glabrata and received at least 1 dose of fluconazole were identified through the electronic query. Chart reviews of these patients followed. The primary outcomes were fungemia eradication and in-hospital mortality. Of the total 124 cases of C glabrata fungemia identified, 54 patient charts were evaluable. Chart review revealed that 65% (17/26) of patients receiving fluconazole as the sole antifungal therapy had successful bloodstream eradication of C glabrata, whereas approximately 54% (15/28) of patients who were changed from fluconazole to an amphotericin B formulation had successful bloodstream eradication. Although no association was found between fluconazole dose and fungemia eradication in the entire study population, higher doses of fluconazole (> or =400 mg/d) were more likely to achieve fungemia eradication than lower doses (< or =400 mg/d) in the subset of patients who received only fluconazole (P = 0.042). Mortality rates were approximately 24% (4/17) and 40% (6/15) in patients having successful bloodstream eradication with fluconazole alone and with fluconazole followed by amphotericin B, respectively, compared with 38% (3/8) in patients with persistent fungemia who received fluconazole alone. Fluconazole was a viable therapy for C glabrata fungemia, with bloodstream eradication in 65% of patients and mortality rates of 24% to 40% in this retrospective chart review.