Comparative activity in vitro of cilofungin (LY 121019) with other agents used for treatment of deep-seated Candida infections.

Cilofungin (LY 121019) is a semi-synthetic lipopeptide antifungal agent that inhibits beta-1,3-D-glucan synthase activity in the cell wall of yeasts. Clinical strains of Candida species were tested for susceptibility to cilofungin and seven other antifungal agents. Candida albicans and Candida tropicalis were susceptible to cilofungin with mean MICs of 0.3 and 0.08 microgram/ml respectively. For most other species the mean MICs were greater than 1-2 micrograms/ml of cilofungin. Studies on the paradoxical growth effect observed with cilofungin in Sabouraud broth showed that, at high concentrations of cilofungin, sufficient damage occurred to make damaged cells highly susceptible to killing by fresh cilofungin. The damaged cells also had increased susceptibility to other antifungal agents to which they were normally resistant. These observations indicate that cilofungin may be a useful agent for the treatment of many invasive Candida infections, either alone or in combination with certain other antifungal agents.