Synergistic effect of terbinafine and amphotericin B in killing Fonsecaea nubica in vitro and in vivo.
Rev Inst Med Trop Sao Paulo. 2019 Jun 19;61:e31
Authors: Zhang J, Wu X, Li M, Huang J, Yin S, Huang H, Lu C, Xi L
Chromoblastomycosis is a chronic fungal infection. Itraconazole and terbinaﬁne 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 terbinaﬁne. 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 terbinaﬁne, amphotericin B, itraconazole, voriconazole and caspofungin were evaluated, as well as the combinations of terbinaﬁne with the other four antifungals. The combined effect of terbinaﬁne and amphotericin B on other 20 clinical F. nubica strains was also evaluated. The minimal inhibitory concentrations of terbinaﬁne, 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 terbinaﬁne and amphotericin B showed the lowest fractional inhibitory concentration index of 0.28 to F. nubica zssy0803 in comparison with combinations of terbinaﬁne and the other four antifungal drugs. The combination of terbinaﬁne and amphotericin B was also synergistic for all the other 20 F. nubica strains. Then, the combination of oral terbinaﬁne (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 terbinaﬁne monotherapy for additional 12 weeks, the patient was cured. These findings indicate for the first time that terbinaﬁne and amphotericin B are synergistic in killing F. nubica both in vitro and in vivo.
PMID: 31241660 [PubMed - in process]