|De Lucca, Anthony|
|Vigo, C - EPA STENNIS SPACE FLT CTR|
|Walsh, T - NATL CANCER INST BETHESDA|
Submitted to: Interscience Conference on Antimicrobial Agents & Chemotherapy Proceedings
Publication Type: Proceedings
Publication Acceptance Date: June 25, 2002
Publication Date: September 27, 2002
Citation: De Lucca II, A.J., Bland, J.M., Boue, S.M., Vigo, C.B., Cleveland, T.E., Walsh, T.J. 2002. Synergy of CAY-1, a Fungicidal Saponin, With Amphotericin B and Itreconazole Against Aspergillus spp and Candida albicans. In: Proceedings of 42nd Interscience Conference on Antimicrobial Agents & Chemotherapy. Abstract F-826. p. 205. Technical Abstract: Background: CAY-1 (mol.wt. 1243), a fungicidal saponin in cayenne (Capsicum fruitescens) is highly lethal for Aspergillus species, Candida albicans, and Pneumocystis carinii below 24.8 ug/ml. To further characterize CAY-1, synergy studies with amphotericin B (AMB) and itraconazole (IT) were performed. Methods: Synergy was determined by the checkerboard microdilution method against nongerminating (NG) and germinating (G) conidia of Aspergillus fumigatus, A. flavus, A. niger and Candida albicans on three separate occasions. Concentrations employed were 0.0-15.5 ug/ml (CAY-1) and 0.075-1.25 ug/ml (AMB and IT). Growth inhibition was observed at 24 and 48 hrs and the Fractional Inhibitory Concentration Index (FICI) calculated. Results: FICI for CAY-1 and AB against NG and G conidia of A. fumigatus at 24 and 48 hrs was 0.78, 0.82; and 0.66, 0.74 respectively. CAY-1 also enhanced AMB activity against NG and G conidia of A. niger at 24 and 48 hrs (FICI: 0.81, 2.0; and 0.91, 0.99, respectively). Similarly, CAY-1 enhanced IT activity against NG and G conidia of A. fumigatus (FICI: 0.89, 0.64; and 0.66, 0.86, respectively at 24 and 48 hrs. CAY-1 also augmented IT activity against the NG and G conidia of A. niger (FICI at 24 and 48 hrs: 0.83, 0.66; and 0.83, 0.58, respectively). There was less synergistic interaction against A. flavus where the predominant effect was indifferent (FICI range: 0.88-2.00). Synergy was observed between CAY-1 and AMB at 24 and 48 hrs against C. albicans (FICI: 0.22 and 0.32, respectively) while CAY-1 and IT interacted indifferently against C. albicans (FICI: 2.0). Conclusion: Overall, CAY-1 displayed additive-synergistic interaction with AMB and IT against the Aspergillus species and excellent synergy with AB against C. albicans. Results indicate CAY-1 may enhance the efficacy of azole and polyene antifungals.