Ketoconazole: a new imidazole antifungal agent has both prophylactic potential and therapeutic efficacy in keratomycosis of rabbits

A highly reproducible quantitative model of fungal infection of the rabbit's corneal stromal was produced using multiple corneal microtrephination. Aspergillus flavus (K4/77), at a concentration of 10(6) spores per ml was systematically implanted into the trephine sites in the cornea, and the degree of corneal infection determined. By pre-inoculation and post-inoculation challenge of these cornea with 1% ketoconazole in arachis oil, the prophylactic potential and the therapeutic usefulness of ketoconazole was determined. Ketoconazole, acetyl-dichlorophenyl-imidazole, has a significant prophylactic potential in inhibiting the development of corneal stromal fungal lesions when it is administered to the cornea of New Zealand white male rabbits as a 1% solution in arachis oil for two consecutive times hourly for two hours before the inoculation of the rabbits cornea with an ocular pathogenic Aspergillus flavus. Ketoconazole also has a therapeutic effect in the reduction of well established A. flavus keratitis in rabbits. When administered as 1% solution in arachis oil for ten consecutive hours daily to well established A. flavus lesions of the cornea of New Zealand albino rabbits, ketoconazole took about sixteen days to cure all the corneal lesions. Finally, using a yeast nitrogen base liquid medium, the in vitro minimal inhibitory concentrations of ketoconazole to twenty-five various human ocular pathogenic fungal isolates were determined and used to recommend those fungi for which ketoconazole would be a good choice for therapy.