New antifungal agents introduced in the millennium include an entirely new class of agent, the echinocandins, active against the fungal cell wall, and the second generation azoles, more potently active against Candida spp.and molds. The echinocandins, of which caspofungin is the only licensed product, inhibit (1,3) íŸ-D-glucan synthase, an enzyme complex necessary for synthesis of a major component of the fungal cell wall. They are fungicidal against all Candida spp. and fungistatic for Aspergillus spp. Available in intravenous form only, they have an excellent safety profile. Caspofungin has been approved for salvage treatment of invasive aspergillosis and for therapy of candidemia and invasive candidiasis of pleural and intraabdominal spaces. Micafungin and anidulafungin, not yet FDA approved, are other echinocandins with similar spectra of activity and safety profiles and currently in clinical trials. They have demonstrated efficacy for esophageal candidiasis, prophylactic antifungal therapy in patients undergoing hematopoietic stem cell transplantation (micafungin), invasive candidiasis and aspergillosis. The extended spectrum triazoles, of which voriconazole is the only licensed product, have potent anti-Candida and filamentous fungi activity. Voriconazole is approved for the primary treatment of invasive aspergillosis, rare mold infections and esophageal candidiasis. It is effective in treatment of candidemia. In case report series, posaconazole is effective in endemic mycoses, invasive candidiasis, and rare mold infections such as fusariosis and zygomycoses. Ravuconazole is not as well studied in clinical trials, but demonstrates potent activity in vitro and in vivo against Candida spp. and filamentous fungi. Drug interactions and liver toxicity may limit the use of the extended spectrum azoles in special circumstances. All of these new agents have clearly added to the antifungal armamentarium and together with the lipid formulation amphotericin B products offer effective and less toxic antifungal therapy. Despite these advances, mortality remains high in immunocompromised patients with invasive fungal infections and challenges for earlier diagnosis, effective anti-fungal strategies and appropriate dosing remain.
Full conference title:
42nd Annual Meeting Infectious Diseases Society of America
- Infectious Diseases Society of America 42nd