Fungal Keratitis Medication
- Author: Daljit Singh, MBBS, MS, DSc; Chief Editor: Hampton Roy, Sr, MD more...
The antifungal agents used include polyenes (eg, natamycin, amphotericin B), azoles (eg, ketoconazole, miconazole, fluconazole, itraconazole), and fluorinated pyrimidines (eg, flucytosine). Amphotericin B is the drug of choice in fungal keratitis caused by yeasts. Natamycin has a broad-spectrum of activity against filamentous organisms. Oral fluconazole and ketoconazole should be considered in the management of deep fungal keratitis.
Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.
Initial drug of choice in Fusarium keratitis. Predominantly fungicidal tetraene polyene antibiotic, derived from Streptomyces natalensis that possesses in vitro activity against a variety of yeast and filamentous fungi, including Candida, Aspergillus, Cephalosporium, Fusarium, and Penicillium species. Binds fungal cell membrane forming a polyenesterol complex that alters membrane permeability, depleting essential cellular constituents. Activity against fungi is dose-related but not effective, in vitro, against gram-negative or gram-positive bacteria.
Generally, therapy should be continued for 14-21 d or until the fungal keratitis has resolved. In many cases, may help to reduce dosage gradually at 4- to 7-day intervals to ensure elimination of the organism.
Polyene antibiotic produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death. First agent of choice in corneal infections due to yeasts, such as Candida species.
Fungistatic activity. Imidazole broad-spectrum antifungal agent; inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.
Often used systemically in the treatment of deep fungal infections. Studies have confirmed intraocular penetration in keratitis due to Fusarium, Aspergillus, Curvularia, and Candida species.
Alternative drug to ketoconazole in the treatment of deep fungal keratitis caused by a variety of fungi. Fungistatic activity. Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.
Converted to fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against Candida and Cryptococcus and generally used in combination with amphotericin B. High incidence of acquired resistance has occurred; therefore, combined treatment with other agents is recommended.
In the treatment of fungal keratitis, polyenes and imidazoles have mostly replaced flucytosine.
Voriconazole is the drug of choice for Aspergillus fumigatus, Aspergillus flavus, Fusarium species, Blastomyces dermatitidis, Coccidioides immitis, Curvularia species, Candida albicans, and Cryptococcus neoformans.
The mode of action is the inhibition of fungal cytochrome P-450, preventing fungal ergosterol biosynthesis, thus damaging the fungal cell wall. A 1% solution is used for local instillation, every hour during the day and every 2 hours during the night.
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