Estudios in vitro e in vivos sobre la actividad de nuevos antifúngicos frente a hongos filamentosos oportunistas

Abstract

In the last decades the frequency and severity of systemic infections by filamentous opportunistic fungi have increased dramatically. Some of these fungi, such as Aspergillus fumigatus, Scedosporium prolificans, Scedosporium apiospermum, Paecilomyces lilacinus and Fusarium spp., are usually refractory to the conventional antifungical therapy. The principal aim of this work was to evaluate the efficacy of new antifungal agents in different animals model in order they can be use as new alternative for the treatment of these severe infections. We developed models of systemic infection in mice, guinea pigs and rabbits which reproduced human infection. We tested experimental therapies with conventional compunds such as amphotericin B (deoxycolate and liposomal), terbinafine or itraconazol and with new compounds such as micafungin, ravuconazole, nikomicin Z or voriconazole. The models of systemic scedosporiosis in rabbits and guinea pigs and paecylomicosis or cerebral aspergillosis in mice, have been described for the first time in this thesis. We demonstrated the efficacy of voriconazole against S. apiospermum in mice and guinea pigs and the efficacy of albaconazole in the treatment of systemic scedosporiosis by S. prolificans in rabbits. It was also demonstrated the high efficacy of micafungin alone or in combination with amphotericin B, itraconazole or nikomicin Z in the treatment of systemic aspergillosis in mice.