Successful treatment of primary cutaneous Aspergillus ustus infection with surgical debridement and a combination of voriconazole and terbinafine

Abstract

Aspergillus ustus infections are associated with a high mortality in immunocompromised hosts, and the mold has decreased susceptibility to most antifungal drugs, especially azoles. We report primary cutaneous A. ustus infection in a patient who failed itraconazole therapy and was switched to voriconazole (VRC). During VRC therapy, the MICs of VRC, amphotericin B (AMB), caspofungin (CFG), and terbinafine (TBF) were 4, 2, 64, and 0.13 μg/mL, respectively. Because the MIC to VRC was high, TBF was added to VRC for synergy based on anecdotal data from other mycoses. After treatment with VRC and TBF for 5 months, MICs of VRC, AMB, CFG, and TBF of A. ustus were 8, 1, 64, and 4 μg/mL respectively. Although the MICs of VRC and TBF increased during antifungal therapy, the patient responded well to the combination antifungal therapy with surgical debridement. With a successful outcome despite high MICs and with limited therapeutic options currently available, we investigated the in vitro activity of posaconazole (PCZ) and VRC individually and in combination with AMB, CFG, or TBF using the fractional inhibitory concentration index (FICI) method. Combination of VRC with TBF showed synergistic activity (FICI = 0.5). Therefore, combination of VRC and TBF with surgical debridement, when appropriate, may be a viable treatment option for refractory A. ustus infections.