NEW APPROACHES TO ANTIFUNGAL THERAPY
Invasive fungal infections are important causes of morbidity and mortality in immunocompromsied hosts.Among the current antifungal compounds approved for treatment of invasive mycoses, most are directed toward ergosterol. Amphotericin B and its lipid formulations interact directly with ergosterol in the fungal cell membrane to increase its permeability. The antifungal imidazoles (miconazole, and ketoconazole) and triazoles (fluconazole and itraconazole) inhibit cytochrome P450-dependent C14-demethylase.The second generation triazoles,voriconazole,posaconazole, and ravuconazole have extended spectrum and potent in vitro and in vivo activity against filamentous fungi.Due to its absence in mammalian cells, the fungal cell wall is a logical antifugnal target. Echinocandins are cell wall-active cyclic lipopeptides that inhibit 1,3-beta glucan synthase.The current genration of echinocandins, caspofungin, micafungin, and anidulofungin,has activity against Candida spp.,Aspergillus spp., and Pneumocystis carinii.Chitin synthase is yet another cell wall target against which nikkomycins are especially active.Combinations of antifungal echinocandins, azoles and nikkomycin Z demonstrate synergy,suggesting the potential utility of simultaneous inhibition of two separate antifungal targets.As the expanding population of immunocompromised patients and the changing patterns of invasive fungal pathogens present evolving challenges to conventional antifungal therapy,this new armamentarium of antifungal compounds will provide important opportunities for novel therapeutic interventions.
Full conference title:
22nd International Congress of Chemotherapy (ICC)