The Role of Voriconazole in the Treatment of Central Nervous System Blastomycosis

Abstract

Background: Blastomycosis is an endemic mycosis caused by the dimorphic fungus Blastomyces dermatitidis. Although this disease primarily involves the lungs, the clinical spectrum of blastomycosis can range from subclinical infection to extrapulmonary dissemination. The central nervous system (CNS) form of blastomycosis is primarily treated with an amphotericin B formulation, but associated toxicities of this agent preclude its use in some patients. Voriconazole is a broad-spectrum triazole antifungal that has emerged as a potential treatment option for CNS blastomycosis because of its excellent penetration into the cerebrospinal fluid and brain tissue. Objective: To evaluate evidence for the use of voriconazole in the treatment of CNS blastomycosis. Data Sources: A literature search was performed using MEDLINE, EMBASE, Cochrane Database, and PubMed (all up to April 2009). Search terms included voriconazole, blastomyces, blastomycosis, CNS, cerebral, and central nervous system. Study Selection and Data Extraction: English-language clinical trials, case reports, treatment guidelines, and background material were searched for voriconazole safety and efficacy data. References of reviewed articles were examined and used to identify additional sources. Data Synthesis: A search of the literature yielded 2 published case reports and 2 case series documenting a total of 7 cases of CNS blastomycosis. In all cases, CNS blastomycosis was successfully treated sequentially with amphotericin B followed by voriconazole. To date, no clinical trials have evaluated the use of voriconazole in treating CNS blastomycosis. Ages of the patients with documented cases of CNS blastomycosis ranged from 14 months to 63 years. In at least 5 cases, CNS blastomycosis presented as lesions in the brain detected by magnetic resonance imaging. One case presented as focal splenic lesions. The remaining 2 were diagnosed based on neuroimaging studies or positive spinal fluid serology. Prior to receiving voriconazole, patients were treated with an amphotericin B formulation combined in some situations with either fluconazole or itraconazole. Subjects underwent treatment with voriconazole for an average of 11 months, with disease remission or stabilization detected in all cases. Conclusions: Further studies are needed to fully elucidate the role of voriconazole in the treatment of CNS blastomycosis. It nonetheless may be considered as an azole option for either follow-up therapy after liposomal amphotericin B therapy or as salvage therapy in patients intolerant of amphotericin B or other azoles.