Relative Efficacies of Anidulafungin, Fluconazole, and amphotericin B for Treatment of Disseminated Candida glabrata in Neutropenic Mice.

T. GUMBO, A. LOUIE, W. LIU, M. DEZIEL, M.F. DRUSANO, G.L. DRUSANO

Author address: 

Ordway Research Institute, Albany, NY.

Abstract: 

Background: Clinical studies suggest a suboptimal response of Candida glabrata (CG) fungemia to fluconazole and amphotericin B-desoxycholate. We evaluated the relative efficacies of fluconazole, amphotericin B and a new echinocandin, anidulafungin, against strains of CG resistant to amphotericin B and fluconazole. Methods: Two CG strains were cultured from patients with invasive candidiasis. MICs for anidulafungin, fluconazole, and amphotericin B were determined by NCCLS macrobroth dilution method in RPMI-1640 with MOPS. Neutropenic mice were infected with CG via the lateral vein and treated with different doses of drugs 4 hours after infection. The end-point was number of CG colonies in the kidney 24 hours after treatment. Results were examined by inhibitory sigmoid Emax modeling with ADAPT II. Results: The MIC for fluconazole for both strains was 128 mg/L. The MIC for amphotericin B were 0.25 and 2 mg/L. The anidulafungin MIC for both strains was 0.1 mg/L. Fluconazole doses achieving up to 600 mg/kg failed to produce a response in either strains. The amphotericin B ED50 was 4.61 mg/kg and Emax decrease was 4.3 Log10 (CFU/g) in the amphotericin B susceptible strain, but there was no decrease in fungal burden for the resistant strain even when amphotericin B doses from 0.5 to 20 mg/kg were given. In mice infected with fluconazole and amphotericin B resistant strain, the anidulafungin ED-50 was 3.18 mg/kg and E-max decrease was 1.67 Log10 CFU (r2=0.δ p
2003

abstract No: 

A-1577

Full conference title: 

43rd Interscience Conference on Antimicrobial Agents
    • ICAAC 43rd