JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS Volume 22, Number 6, 2006 © Mary Ann Liebert, Inc. Voriconazole and Fungal Keratitis: A Report of Two Treatment Failures JOANN A. GIACONI, FABIANA B. MARANGON, DARLENE MILLER, and EDUARDO C. ALFONSO ABSTRACT Two cases of fungal keratitis, one caused by Fusarium oxysporum and the other by Col- letotrichum dematium, that failed treatment with topical voriconazole 1% are presented. These cases are noteworthy in that topical voriconazole was unable to eradicate the corneal infec- tion in both cases, despite relatively low MIC 90 tested for each species of 8 and 1 g/mL, re- spectively. 437 INTRODUCTION V ORICONAZOLE, ONE OF THE NEWER TRIAZOLES, is considered fungicidal against many molds, 1 and it is marketed for use against invasive As- pergillus, Scedosporium apiospermum and Fusarium oxysporum spp. infections. Two (2) patients with fungal keratitis presented to the Bascom Palmer Eye Institute (Miami, FL) in 2002, and owing to the reported success of voriconazole in oph- thalmic cases, 2,3 we offered topical voriconazole as treatment. We report the failure of voricona- zole to effectively treat these infections, and sensitivity testing data relating to this medication. CASE REPORTS An 80-year-old man was referred after 2 weeks of empiric treatment with topical steroids, an- tibiotics, and antivirals for eye irritation. After our initial examination (Fig. 1a), corneal scrap- ings were taken that grew F. oxysporum within 3 days. Topical voriconazole 1% in normal saline every hour was offered as a new treatment with informed consent. Given the intensity of inflam- mation, oral voriconazole was also offered, but the patient declined owing to its expense. One (1) week later, there was clinical improvement, with decreasing density of the infiltrate and resolution of the hypopyon, so topical voriconazole was de- creased to every 3 h, whereas corneal scrapings were continued regularly at each visit to help corneal penetration. Three (3) days later, the pa- tient’s condition worsened. Therapeutic pene- trating keratoplasty was discussed but delayed because of elevated intraocular pressure. Hourly natamycin 5% was added to his regimen, and voriconazole was increased again to every hour. The following week, worsening discomfort and vision merited a transplant. The corneal button grew F. oxysporum despite 3 weeks of topical voriconazole and 10 days of topical natamycin treatment (Fig. 1b). In vitro susceptibility of the isolate to voriconazole was 8 g/mL (Fungal Testing Lab, San Antonio, TX). There has been no recurrence of infection since keratoplasty. Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Mi- ami, FL. None of the authors has any financial or proprietary interest in materials or methods discussed.