Influence of Voriconazole and Fluconazole on Reconstituted Esophageal Epithelium Infected by Candida albicans.



Background: We studied the influence of voriconazole and fluconacole on reconstituted esophageal epithelium being infected by Candida albicans. Methods: Reconstituted esophageal epithelium (SkinEthic Lab., Nice, France) was grown in a chemically defined medium on inert polycarbonate filters. We infected the tissue on the top with 2x106 cfu of C. albicans SC5314. We added voriconazole to the maintenance medium underneath the filter in concentrations of 2 mg/l and 16 mg/l respectively or fluconazole (32 mg/l). Histological sections were done at different times. In a control group we performed sections of infected tissue without antimycotics and also of non-infected tissue. Results: In non-infected epithelium we could see a normal growth and closed cell formation within four days. The control histology for the infection model demonstrated a good growth at 4 h after infection. After 8 h hyphae penetrated the tissue to 2/3, a destruction of the tissue began after 28 h. On the surface of the epithelium a thick layer of fungal cells was developed. After 60 to 84 h the tissue was destroyed. We saw a growth of mycelia in plaque-like structure on the surface before invading the tissue. Voriconazole was very effective to reduce the growth of Candida on the cell surface and prevented the penetration of hyphae into the tissue if it was given 4 till 8 h after infection. After input of voriconazole at 16 to 24 h the infiltration stopped more slowly. 36 h after infection voriconazole could not stop the destruction of the epithelium despite of reducing the fungi. The results with fluconacole were the same in principle, but not so distinct. Conclusions: The reconstituted esophageal epithelium appears as a good basis to test the impact of antimycotics. They were able to stop or reduce the invasion of hyphae. The effect of voriconazole was stronger compared with fluconazole.

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42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 42nd