Combining two antifungal agents does not enhance survival of Galleria mellonella larvae infected with Madurella mycetomatis.

Abstract

To determine whether combination therapy would improve therapeutic outcome in eumycetoma caused by Madurella mycetomatis. Survival, colony-forming units (CFU), melanisation and histopathology in M. mycetomatis-infected Galleria mellonella larvae treated with amphotericin B, itraconazole, terbinafine or combinations thereof were determined. Compared to larvae treated with 5% glucose, enhanced survival was obtained when M. mycetomatis-infected larvae were treated with amphotericin B, but not when they were treated with itraconazole or terbinafine. Combination therapy did not increase survival compared to 5% glucose-treated larvae, itraconazole-treated larvae or terbinafine-treated larvae. Compared to amphotericin B monotreatment, a significant decrease in survival was noted when this therapy was combined with either itraconazole or terbinafine. CFU, melanisation and histopathology did not differ between monotherapy, combination therapy or 5% glucose-treated larvae. Combining different classes of antifungal agents did not enhance the survival of M. mycetomatis-infected G. mellonella larvae. Instead of improving the therapeutic outcome, combining either itraconazole or terbinafine with amphotericin B resulted in significantly lower survival rates of infected larvae than amphotericin B monotherapy. This experimental study does not provide support for the use of combined amphotericin B and itraconazole, combined itraconazole and terbinafine or combined terbinafine and amphotericin B and should be confirmed in other animal models.