Antifungal research and development are challenging, some new products are progressing in development. Azoles: Albaconazole (UR-9825) is currently under development and the orally active agent has shown efficacy in animal models of infections caused by Aspergillus, Candida, Cryptococcus and Scedosporium spp. Ravuconazole (BMS-207147) no longer seems to be under active development and an intravenous formulation has not been developed. Isavuconazole is currently in Phase III clinical trials. Polyenes: A cochleate formulation of amphotericin B has shown efficacy in experimental models of candidiasis and aspergillosis. The formulation promises oral bioavailability of amphotericin B. A liposomal formulation of the tetraene nystatin has undergone testing preclinically and in clinical trials. Sordarins: Sordarin R-135853 has shown in vivo efficacy in various experimental models of candidiasis. Echinocandins: Development of new agents in this class is slow, and there is only one candidate in early preclinical development: aminocandin (IP960/HMR3270). This agent has shown good in vivo and in vitro activity against Candida spp. and filamentous fungi. Nanoparticle preparations: Various nanoparticle formulations of amphotericin B that have shown good in vitro and in vivo activity with decreased toxicity. Nanoparticle formulations of itraconazole have also been developed and are currently under investigation. Nikkomycin Z: Nikkomycin Z is to competitively inhibit chitin synthases and thereby interfere with fungal cell wall construction. Antibodies: Protective monoclonal Antibodies (mAbs) have now been described to Cryptococcus neoformans, C. albicans, Histoplasma capsulatum, Aspergillus fumigatus, Paracoccidiodes brasiliensis and Sporothrix shenkii. Studies with mAbs also revealed the existence of both protective and non-protective antibodies to fungal pathogens, which provided a possible explanation for the inconclusive results in passive-antibody experiments with immune sera. Vaccines: The scientific appeal of preventing fungal infections by vaccination is most obvious for endemic dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., H. capsulatum and P. brasiliensis) as exposures to these pathogens usually result in long-term immunity. A vaccine to prevent candidaemia has been launched recently. Prophylactic vaccines are intriguing but only offer protection against selected organisms.
Full conference title:
22nd European Congress of Clinical Microbiology and Infectious Diseases
- ECCMID 22nd (2012)