Treatment of Blastomycosis with Fluconazole: A Pilot Study

Abstract

There are few clinical data concerning the use of fluconazole, a triazole antifungal agent with in vitro activity against Blastomyces dermatitidis, in the treatment of human blastomycosis. We conducted a multicenter, randomized, open-label pilot trial comparing two daily doses of fluconazole (200 mg and 400 mg) in the treatment of non-life-threatening, non-CNS blastomycosis. Twenty-four patients were enrolled in the study, and 23 patients were evaluable for efficacy analysis. Overall, treatment of 15 (65%) of 23 patients was successful, including eight (62%) of 13 who received 200 mg daily and seven (70%) of 10 who received 400 mg daily. The mean duration of therapy for successfully treated patients was 6.7 months. Of the six patients whose prior antifungal therapy had failed, all six eventually responded to fluconazole treatment. We conclude that fluconazole (200 mg to 400 mg daily) given for at least 6 months is moderately effective treatment for blastomycosis.

Susceptibilities of Clinical and Laboratory Isolates of Blastomyces dermatitidis to Ketoconazole, Itraconazole, and Fluconazole

“…While these in vitro results correlate with the clinical efficacies noted to date with these agents in the treatment of blastomycosis, in vitro susceptibilities do not necessarily reflect in vivo responses to therapy. Specifically, fluconazole at doses of Յ200 mg/day has been less effective than either ketoconazole (400 mg/day) or itraconazole (200 mg/day) (3,4,13). Our study demonstrates that itraconazole and ketoconazole have comparable in vitro activities, and both have superior in vitro activities compared to that of fluconazole.…”

“…Unfortunately, the utility of this therapy is limited by its side effect profile (2). Fluconazole at doses of 200 to 400 mg appears less efficacious, with cure rates of 62 and 70%, respectively, having been reported (13). However, a recent study reported successful treatment in 89 and 85% of patients who received 400 and 800 mg, respectively (14).…”

Antifungal Clinical Trials and Guidelines: What We Know and Do Not Know

“…Indeed, itraconazole remains the drug of first choice for mild to moderate non-CNS disease based on these data and extensive clinical experience. Studies exploring fluconazole 400 mg and 800 mg daily for treatment of histoplasmosis and blastomycosis, respectively, suggested that fluconazole was a poor alternative to itraconazole for non-CNS disease (McKinsey et al 1996;Wheat et al 1997), but it was an acceptable agent for CNS blastomycosis attributable to its favorable pharmacokinetics (Pappas et al 1995(Pappas et al , 1997.…”

Practice Guidelines for the Management of Patients with Blastomycosis

“…The role of fluconazole in the treatment of blastomycosis is limited. The results of a small pilot study of 200-400 mg/d of fluconazole were disappointing, with a successful outcome noted only for 15 (65%) of the 23 patients [17]. A recent study of higher dosages of fluconazole (400-800 mg/d) showed enhanced efficacy [18]; a successful outcome was noted for 34 (87%) of 39 patients treated for a mean duration of 8.9 months.…”