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Chromoblastomycosis is a chronic fungal infection. Itraconazole and terbinane are the most recommended antifungal drugs for chromoblastomycosis, while amphotericin B is not usually recommended. A patient with chromoblastomycosis in our hospital showed poor clinical responses to itraconazole and terbinane. The fungus isolated from the lesions of this patient was identified as Fonsecaea nubica and numbered zssy0803. In vitro antifungal susceptibilities of F. nubica zssy0803 to terbinane, amphotericin B, itraconazole, voriconazole and caspofungin were evaluated, as well as the combinations of terbinane with the other four antifungals. The combined effect of terbinane and amphotericin B on other 20 clinical F. nubica strains was also evaluated. The minimal inhibitory concentrations of terbinane, amphotericin B, itraconazole, voriconazole and caspofungin on F. nubica zssy0803 were 0.25 μg/mL, 2 μg/mL, 1 μg/mL, 4 μg/mL and 8 μg/mL, respectively. The combination of terbinane and amphotericin B showed the lowest fractional inhibitory concentration index of 0.28 to F. nubica zssy0803 in comparison with combinations of terbinane and the other four antifungal drugs. The combination of terbinane and amphotericin B was also synergistic for all the other 20 F. nubica strains. Then, the combination of oral terbinane (500 mg/day) and intralesional injections of amphotericin B (1 mg/mL) was used to treat this patient. After this combined therapy for 25 weeks and terbinane monotherapy for additional 12 weeks, the patient was cured. These findings indicate for the first time that terbinane and amphotericin B are synergistic in killing F. nubica both in vitro and in vivo.

Synergistic effect of terbinafine and amphotericin B in killing Fonsecaea nubica in vitro and in vivo