Comparative efficacies of cilofungin (Ly121019) and amphotericin B against disseminated Candida albicans infection in normal and granulocytopenic mice

Abstract

The efficacies of cilofungin (Ly121019), a semisynthetic lipopeptide antifungal agent, and amphotericin B in the treatment of disseminated candidiasis in normal and neutropenic mice were compared. In mice infected with 2 X 106 CFU of Candida albicans, treatment with cilofungin in twice-daily doses of 25 or 35 mg/kg of body weight by intraperitoneal injection for 10 days gave survival rates of 83 and 90%. In contrast, there was 97% mortality in infected controls receiving 2 x 106 CFU intravenously and 93% survival in mice treated with 1 mg of amphotericin B per kg once a day. Mice rendered granulocytopenic by the administration of cyclophosphamide showed survival rates of 83 and 80%o when treated with 25 or 35 mg of cilofungin per kg for 10 days compared with 43% survival rate in mice treated with 1 mg of amphotericin B per kg (P = 0.0030 and P = 0.0080, respectively). Similar results were obtained when the two antifungal agents were administered for a period of 30 days. Administration of 25 or 35 mg of cilofungin per kg twice a day to granulocytopenic mice receiving 106 CFU of C. albicans gave survival rates of 93% and 93% compared with 53% survival with amphotericin B. With 15 mg of cilofungin per kg twice a day for 10 days, a survival rate of 43 to 50%o was observed in both normal and granulocytopenic mice compared with 56 and 60%, respectively, when this dosage was continued for 30 days. Cilofungin eradicated C. albicans from the kidneys, spleens, and livers of surviving animals. No toxic effects were observed with any of the dosage regimens used. The clearance of C. albicans from the kidneys, spleens, livers, and brains in normal mice was studied following infection with 5 x 105 and 1 x 105 intravenously. The mice in the treatment groups received 25 mg of cilofungin per kg twice a day for 10 days. In 8 to 12 days, this treatment was able to clear the organisms from the kidneys, spleens, and livers of mice infected with 5 x 105 C. albicans. Mice infected with 105 C. albicans and treated with cilofungin (25 mg/kg)

Current and Emerging Azole Antifungal Agents

“…Although the first agent with antifungal activity, griseofulvin, was isolated in 1939 (28) and the first azole and polyene antifungal agents were reported in 1944 and 1949, respectively (85), it was not until 1958 that oral griseofulvin and topical chlormidazole became available for clinical use (Fig. 1) (13,21,28,41,85,94,103,109,132,133,151,250,274). The introduction of griseofulvin was followed in 1960 by that of amphotericin B (109), which is still the "gold standard" for the treatment of severe systemic mycoses (94).…”

Antifungal Activity of LY295337 in vitro against Clinical Isolates of <i>Candida </i>spp.

“…We also compared our results with those obtained by Khardori et al [16], who studied the efficacy of another antifungal agent of the same group, cilofungin (LY121019), and ob served that LY295337 is active against all the species of Candida, in contrast to cilofungin, which possesses maximum activity against C. albicans and C. tropical is, C. parapsilosis being the least sensitive to cilofungin.…”