Ketoconazole Therapy for Endemic Blastomycosis

Abstract

Amphotericin B is effective in therapy for blastomycosis but causes a number of serious adverse reactions. Because ketoconazole has in-vitro activity against Blastomyces dermatitidis, we administered this agent in a dosage of 400 mg/d to 46 patients with blastomycosis, with 43 patients receiving at least 1 month of therapy. Thirty-five patients had cure without relapse over a mean follow-up of 17 months. Six had a relapse of infection but 4 of these had been noncompliant with therapy. Two patients improved initially but ultimately had progression of disease despite maintenance of adequate serum levels. Adverse effects were common but not severe. Three patients with extensive infection died--2 had received only one dose of ketoconazole and 1 had received therapy for only 2 weeks. The cure rate in these patients suggests that ketoconazole may replace amphotericin B as the initial treatment of blastomycosis that is not overwhelming.

Blastomycosis of the lumbar spine: case report and review of the literature, with emphasis on diagnostic laboratory tools and management

“…Some are of the opinion that in immunocompetent patients with uncomplicated pulmonary forms of the disease, therapy may not be necessary [6,27,32]. Considering the complication of blastomycosis and the relative safety of oral antifungal medication, we tend to agree with others [3,10,18], that when blastomycosis is suspected, even in its mildest form (as in the case of our healthy patient), antifungal therapy should be instituted.…”

“…Bone scan with 67 Ga was not suggestive of any active infectious process in the skeleton. The Westergren sedimentation rate was 7 mm/h and WBC count was 5,700 × 10 3 /mm 3 . A transpedicle biopsy using the appropriate technique that was published elsewhere [15] failed to isolate any blastomyces.…”

“…The adjacent discs were not involved with the infection, which was traveling via the left psoas muscle. Blood samples at admission showed a sedimentation rate (Westergren) of 60 mm/h and a white blood cell (WBC) count of 9,800 × 10 3 /mm 3 .…”

Synergy of itraconazole with macrophages in killing Blastomyces dermatitidis

“…Less information is available concerning the interaction of the newer antifungal agents, the oral azoles, with host immune responses (1, 3, 7, 8, 10, 14, 16-19, 21, 22). We became interested in the possible effects of itraconazole on cellular immunity because of this triazole's efficacy against experimental murine blastomycosis (2) and human blastomycosis (4,11,20) and indications of superior in vivo efficacy of itraconazole compared with ketoconazole (2, 4) against blastomycosis, which was not predicted from either inhibition or killing of B. dermatitidis (2) (CTCM) consisted of 79 ml of RPMI 1640, 10 ml of fetal bovine serum, 10 ml of fresh mouse serum, and 1 ml of penicillin-streptomycin. Ketoconazole and itraconazole were supplied as powders by Janssen Research and Development, New Brunswick, N.J. Itraconazole (10 mg) was dissolved in 1 ml of a solution consisting of 50% acetone and 50% 0.2 N HCI.…”

“…Less information is available concerning the interaction of the newer antifungal agents, the oral azoles, with host immune responses (1, 3, 7, 8, 10, 14, 16-19, 21, 22). We became interested in the possible effects of itraconazole on cellular immunity because of this triazole's efficacy against experimental murine blastomycosis (2) and human blastomycosis (4,11,20) with L-glutamine, heat-inactivated fetal bovine serum, and penicillin-streptomycin (10,000 U/ml and 10,000 ,ug/ml, respectively) were purchased from GIBCO Laboratories (Grand Island, N.Y.). Complete tissue culture medium * Corresponding author.…”