Objective: To determine whether combination therapy would improve therapeutic outcome in eumycetoma caused by Madurella mycetomatis.
Methods: 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.
Results: 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.
Conclusions: 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.

Additional Metadata
Keywords Animal model, Azole terbinafine grain, Combination therapy, Eumycetoma
Persistent URL dx.doi.org/10.1111/tmi.12871, hdl.handle.net/1765/99804
Journal Tropical Medicine & International Health
Citation
Eadie, K, Parel, F, Helvert-van Poppel, M, Fahal, A.H, & van de Sande, W.W.J. (2017). Combining two antifungal agents does not enhance survival of Galleria mellonella larvae infected with Madurella mycetomatis. Tropical Medicine & International Health. doi:10.1111/tmi.12871