VAZQUEZ JA, NAGAPPAN V, BOIKOV D; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. M-1509.
Wayne State University School of Medicine, Detroit, MI
BACKGROUND: The medically important fungi are in a state of flux. Candida albicans is being replaced by many of the non-albicans Candida species, especially Candida glabrata which is less susceptible to all antifungals. Caspofungin acetate (Cancidas) (Cfg) is the newest antifungal approved for the Tx of fungal infections. The objective was to evaluate the in-vitro activity of Cfg against C. glabrata. METHODS: 50 clinical isolates of C. glabrata were evaluated by MICs, MFCs and time kill assays. The assays were performed using NCCLS broth microdilution methodology and compared with amphotericin B (AB), fluconazole (FLZ) and voriconazole (VCZ). Additionally, synergy studies using checkerboard methodology were performed. RESULTS: Cfg showed excellent in-vitro activity against C. glabrata with MICs (range 0.125 - 1 microg/ml; MIC[50] 0.5/MIC[90] 1 microg/ml) and MFCs for C. glabrata (range 0.5 - 4 microg/ml; MFC[50] 1/MFC[90] 2) that showed fungicidal activity. In comparison, the in-vitro activity for AB, FLZ, and VCZ were 0.06 - 1, 0.03 ->16, and 2 - >64 microg/ml, respectively. The MFC ranges for AB, FLZ, VCZ were 0.125 - 1, >32 and > 128 microg/ml, respectively. Time kill assays evaluating 1 FLZ-resistant and 1 FLZ-susceptible strain of C. glabrata showed excellent fungicidal activity at 2 hrs with Cfg kill rates of > 99.9%. Synergy studies reveal excellent synergistic activity with Cfg + Flz, an additive effect using Cfg + VCZ, and indifference to additive effect with Cfg + AB. CONCLUSIONS: In-vitro assays with Cfg demonstrated excellent fungicidal activity against C. glabrata, including FLZ- and VCZ-resistant strains. In addition, time kill assays also demonstrated excellent fungicidal against C. glabrata by 2 hrs. Combination assays demonstrate excellent synergistic activity, especially with Cfg and either FLZ or VCZ, and indifference with AB. Cfg may be considered a possible alternative antifungal agent alone or in combination for difficult to treat C. glabrata infections.
Publication Types:
Keywords:
- Amphotericin B
- Antifungal Agents
- Biological Assay
- Candida
- Candida albicans
- Candida glabrata
- Fluconazole
- In Vitro
- Microbial Sensitivity Tests
- Peptides, Cyclic
- Pyrimidines
- Triazoles
- caspofungin
- methods
- voriconazole
Other ID:
UI: 102266970
From Meeting Abstracts