Invasive aspergillosis (IA) has become a leading cause of death in patients with hematologic malignancies undergoing intensive chemotherapy or stem cell transplantation as well as in organ transplant patients. Early diagnosis of IA is of outstanding importance because the chance of cure depends on prompt institution of systemic antifungal treatment. For three decades, amphotericin B deoxycholate (DAmB) has been the standard for first-line treatment of IA. Because of its poor tolerability and significant nephrotoxicity, D-AmB is often withheld or administered at suboptimal doses and/or terminated prematurely, so that treatment results with D-AmB have been disappointing. New treatment options are provided by the introduction of the echinocandins, a new class of antifungals inhibiting B-1,3-glucan synthesis in the fungal wall, which represents a distinct target from azole antifungals, flucytosine, and polyenes.Their in-vitro activity and their preclinical efficacy focus on fungal pathogens with a high proportion of B-1,3-glucan in their cell wall, i.e., Candida spp. and Aspergillus spp., whereas infections from Fusarium spp. or Mucor spp. are not susceptible to antifungal monotherapy with an echinocandin. Caspofungin (MK-0991) has recently been approved for second-line therapy in patients with IA. A 40 to 50% partial or complete response to caspofungin was observed in patients intolerant or refractory to AmB or other licensed antifungals active against Aspergillus spp. The safety and tolerability of echinocandins is favorable, because these substances do not interact with the cytochrome ~450 isoenzyme system and are not associated with nephrotoxicity or serious infusion-related adverse events. Caspofungin has been studied in patients with esophageal and oropharyngeal candidiasis, and has shown at least equivalent efficacy as AmB and fluconazole. In a prospective, double-blind study in patients with disseminated candidiasis, it has shown response rates well comparable with AmB. Micafungin has been given in small groups of patients with invasive candidiasis, and has shown encouraging results as well. Of note, the echinocandins offer an interesting new option of synergistic treatment when combined with voriconazole or AmB. At present, there are insufficient data to assess the efficacy of the echinocandins in the first-line treatment of IA. With respect to their very favorable safety profile, echinocandins may be excellent candidates for very early empirical or pre-emptive antifungal treatment in patients at risk for invasive fungal infections.
Full conference title:
12th International Symposium on Infections in the Immunocompromised Host
- ISIIH 12th