info:eu-repo/semantics/article
In Vitro and In Vivo Evaluation of Voriconazole-Containing Antifungal Combinations against Mucorales Using a Galleria mellonella Model of Mucormycosis
Fecha
2019-01Registro en:
Macedo, Daiana; Leonardelli, Florencia; Dudiuk, Catiana Beatriz; Vitale, Roxana Gabriela; del Valle, Eleodoro Eduardo; et al.; In Vitro and In Vivo Evaluation of Voriconazole-Containing Antifungal Combinations against Mucorales Using a Galleria mellonella Model of Mucormycosis; Multidisciplinary Digital Publishing Institute; Journal of Fungi; 5; 1; 1-2019; 1-12
2309-608X
CONICET Digital
CONICET
Autor
Macedo, Daiana
Leonardelli, Florencia
Dudiuk, Catiana Beatriz
Vitale, Roxana Gabriela
del Valle, Eleodoro Eduardo
Giusiano, Gustavo Emilio
Gamarra, Soledad
García Effron, Guillermo
Resumen
Mucorales are resistant to most antifungals. Mucormycosis associated mortality is unacceptable and new treatment approaches are needed. The objectives of this work were (i) to evaluate the nature and intensity of the in vitro effect of three drugs combinations which included voriconazole (plus amphotericin B, posaconazole and caspofungin) against 25 strains of six different Mucorales species; (ii) to evaluate a Galleria mellonella mucormycosis model; and (iii) to establish if any in vitro?in vivo correlation exists. As expected, amphotericin B and posaconazole were the most active drugs when tested alone. However, species-specific differences were found. The ΣFICs varied according to the used combination. Only five strains showed synergism when voriconazole was combined with posaconazole and three strains when combined with amphotericin B. Microscopic hyphae alteration were observed for some isolates when confronted against drugs combinations. Using a Galleria mellonella mucormycosis model, better survival was seen in voriconazole plus amphotericin B and plus caspofungin combined treatments when compared with AMB alone for R. microsporus. These survival improvements were obtained using a 32-fold lower amphotericin B doses when combined with VRC than when treated with the polyene alone. These lower antifungal doses emulate the antifungal concentrations where the microscopic hyphae alterations were seen.