Blastomycosis

Figure 178.1 Histopathology of blastomycosis of skin. Cell of Blastomyces dermatitidis undergoing characteristic broad-based budding, surrounded by neutrophils. Multiple nuclei are visible. (Public Health Image Library, Centers for Disease Control and Prevention [CDC].)

Treatment

Presently, three drugs are approved for the treatment of blastomycosis: amphotericin B, itraconazole, and ketoconazole. Traditionally, amphotericin B has been the mainstay of therapy for all forms of blastomycosis, but studies and experience gained since the early 1990s indicate that ketoconazole, itraconazole, and fluconazole are highly effective alternative oral therapies. It was recently recommended that ketoconazole no longer be manufactured for systemic use because of hepatotoxicity concerns, so it is unclear if this compound will remain available to clinicians. More recently, voriconazole has emerged as an effective alternative to the older azoles, especially for patients with complicated disease involving the CNS. Although no comparative trials have been performed, itraconazole appears to have greater efficacy and less toxicity than either fluconazole or ketoconazole, and therefore is the oral agent of choice. In a recently published trial, 95% of patients with non-life-threatening, non-CNS blastomycosis were treated successfully with itraconazole, 200 to 400 mg daily for 2 to 6 months. This approximates the observed efficacy seen with amphotericin B. Clinical data regarding the use of fluconazole suggest similar efficacy of this agent, with at least 80% of patients responding to 400 to 800 mg daily for 6 months. Most patients with blastomycosis can be started on oral itraconazole, 200 mg daily and advanced by 100-mg increments at monthly intervals to a maximum of 400 mg daily in patients with persistent or progressive disease. In patients with more aggressive disease, an initial dose of 400 mg is appropriate. Therapy with any of the azoles should be given for a minimum of 6 months. Clinical experience with posaconazole is very limited in all forms of blastomycosis; however, based on in vitro susceptibility data, one would anticipate excellent clinical activity of this compound.

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