Synergistic effects of terbinafine and itraconazole on clinical isolates of Fonsecaea monophora.

Our objective was to develop new approaches to the chemotherapy of invasive infections caused by Fonsecaea monophora. The in vitro effects of a combination of terbinafine with itraconazole on 18 clinical isolates were evaluated using a checkerboard microdilution method. The mode of interaction between the two drugs on the 18 isolates was analyzed using fractional inhibitory concentration index (FICI) analysis. FICI analysis demonstrated that 12 (67%) were synergistic, 4 (22%) were additive, and 2 (11%) were indifferent, with no antagonism being observed. The minimal inhibitory concentrations (MICs) obtained with the terbinafine-itraconazole combination were within levels that can be achieved in plasma at clinically relevant doses. Our results indicate the terbinafine-itraconazole combination may be an effective therapy for Fonsecaea monophora infection, which should be tested in clinical setting with patients with this disease.