There are only a few antifungal agents known to be effective against invasive pulmonary aspergillosis (IPA). Amphotericin B (Amph-B) has traditionally been the first line antifungal agent, and its lipid formulations were developed to decrease the renal toxicity associated with Amph-B. An azole, itraconazole, may be an option. However, in seriously ill patients, Amph-B or the lipid formulations are recommended because of the more potent antifungal activity. Other potential agents currently in development to treat this problematic infection may be lipopeptides, which include FK 463, caspofungin and V-ecchinocandin. This class of antifugals shows activity comparable to Amph-B against Aspergillus spp. with much less toxicity. The mode of action of the lipopeptides is the inhibition of 1,3-beta-D-glucan synthase. Since this is a different mechanism of action from that of Amph-B, the combination of the lipopeptides with Amph-B could show potent synergism. We tested the synergistic effect of FK463 with Amph-B in clinical isolates of A. fumigatus, and have observed in vivo efficacy in murine IPA. We have also observed clinical efficacy of FK463. The drug has been used in the treatment of IPA in non-neutropenic patients, and in a patient with sequential positve blood cultures who showed significant improvement.
Full conference title:
22nd International Congress of Chernotherapy (ICC)
- ICC 22nd