Antifungal therapies in murine disseminated phaeohyphomycoses caused by Exophiala species

Objectives: We have evaluated the efficacy of posaconazole, itraconazole and amphotericin B in murine models of disseminated infection caused by Exophiala spp. Methods: Immunosuppressed mice were treated with posaconazole at 10, 20 or 40 mg/kg/day orally (po), amphotericin B at 1.5 mg/kg/day intraperitoneally (ip) or itraconazole at 50 mg/kg/day po. Treatment began 1 day after infection and continued for 7 days post-infection. Two strains of each of the three most relevant clinical species, i.e. Exophiala dermatitidis, Exophiala oligosperma and Exophiala xenobiotica, were tested. Results: Posaconazole showed the highest efficacy in mice infected with E. dermatitidis, the only species that showed a high neurotropism, while the three drugs showed a similarly good activity against E. oligosperma and E. xenobiotica infections. Conclusions: The results suggest that posaconazole may have a clinical role in the treatment of disseminated infections caused by Exophiala species, especially in those with CNS invasion.