The in vitro activity of sordarins: GM 193663, GM 222712 and GM 237354, alone and in combination with other antifungal agents such as Amphotericin B (AmB), Fluconazole (Flu), Itraconazole (Itr) and Voriconazole (Vor) was evaluated against clinical isolates of Candida albicans, Aspergillus spp. and Scedosporium apiosperinum. In vitro susceptibility was tested using the NCCLS microdilution assay and combination studies were done by (i) the checkerboard method by broth microdilution (ii) in agar dilution with sub-inhibitory concentrations of AmB and Itr and a range of sordarin concentrations; and (iii) in agar cross-diffusion assays with multipoint inoculator or trench procedure. Against C. albicans GM 193663 (MIC:0.008 gg/ml) and GM 237354 (MIC:0.001 gg/ml) interact sinergically (>= 2fold reduction in MIC of each drug in combination compared with when tested alone) with AmB and Itr, and has an additive effect in combination with Flu. The combination of GM 222712 with sub-inhibitory concentrations of AmB and Itr resulted in a synergic effect against A. flavus and an additive effect against A. fumigatus. The combined effect of GM 237354 with AmB and Itr show additivity against both species of Aspergillus. On Scedosporium apiospermum, GM 222712 and GM 237354 only have additive effect with AmB, Itr and Vor. Generally, sordarins produced synergy or additivity when combined with other systemic antifungal agents. However, no increase in toxicity was observed when the same combinations were tested on mammalian cell lines.
Full conference title:
38th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 38th