Actividad in vitro e in vivo de nuevos antifúngicos frente a hongos oportunistas

Identificador:  TDX:508

Handle: https://hdl.handle.net/20.500.11797/TDX508

Autores:  Serena Perelló, Carolina

Resumen:
The conventional antifungal therapies commonly used for the treatment of systemic fungal infections due to opportunistic pathogenic yeasts are far to be the optimal. These infections affect mainly immunocompromised patients, causing high mortality rates. Although Candida spp. are the most common cause of fungal infections, other genera such as Cryptococcus, Trichosporon, Blastoschizomyces, Rhodotorula and Sporobolomyces, have also frequently reported. In general, these latter genera are less susceptible to conventional antifungal treatments and the number of in vitro and in vivo studies about the efficacy of new antifungal treatment against them is very scarce. The main objective of this thesis is to evaluate both in vitro and in animal models the efficacy of new therapeutical strategies. We have evaluated the in vitro activity of micafungin combined with amphotericin B against 115 strains belonging to the seven species of Candida most commonly found in clinical samples (20 of C. albicans, 20 of C. dubliniensis, 15 of C. glabrata, 20 of C. krusei, 10 of C. lusitaniae, 15 of C. parapsilosis and 15 of C. tropicalis).. When we used the MIC-2 endpoint criterion such combination showed synergism against all the species tested. We have evaluated the in vitro activity of micafungin combined with each of the following drugs: amphotericin B, fluconazole, itraconazole, voriconazole and ravuconazole, against 37 strains belonging to the four most clinically relevant species of Cryptococcus i.e. C. neoformans, C. gattii, C. albidus and C. laurentii. The combination micafungin with amphotericin B showed the best synergism, with 70% of synergistic interactions. Voriconazole showed an excellent activity in a murine model of central nervous system infection by Cryptococcus neoformans.