Topical Caspofungin for Treatment of Keratitis Caused by Candida albicans in a Rabbit Model

Abstract

Candida albicans is the most frequent cause of fungal keratitis in temperate regions. Caspofungin has potent activity against Candida spp. in a variety of clinical settings. Little is known, however, about its activity against fungal keratitis. We compared the efficacy of topical caspofungin with that of topical amphotericin B (AMB) in a rabbit model of experimental keratomycosis. Keratitis was induced with a standardized inoculum of Candida albicans (SC 5314) placed on the debrided cornea. Twenty-four hours after infection, animals were randomly assigned to treatment with 0.15% caspofungin, 0.5% caspofungin, 0.15% AMB, and a saline control (n ‫؍‬ 12 rabbits in each group). For the first 12 h, treatment was repeated every 30 min and, after a 12-h pause, was resumed at hourly intervals for another 12 h. The animals were examined and killed 12 h after administration of the last dose. Treatment effects were evaluated by clinical assessment, fungal culture, and histopathology. Drug treatment significantly reduced corneal fungal recovery from 3.78 log 10 CFU in saline-treated animals to 2.97, 1.76, and 1.18 log 10 CFU in animals treated with 0.15% caspofungin, 0.5% caspofungin, and 0.15% AMB, respectively. By histopathology, the mean hyphal density was significantly lower in the corneas of treated animals than in those of the controls; there was no difference in hyphal densities between the different treatment groups. The depth of corneal invasion was not significantly reduced by the antifungal treatments. By clinical assessment, keratitis progressed in animals treated with saline, whereas disease progression was inhibited by all drug treatment regimens. In our rabbit model, 0.5% caspofungin was as effective as 0.15% AMB for the topical treatment of Candida keratitis. The potential clinical efficacy of caspofungin awaits further investigation.

Liposomes as an ocular delivery system of fluconazole: in‐vitro studies

“…In particular, the treatment of keratomycosis is often frustrating because of the limited tissue penetration, narrow antimicrobial spectrum and toxicity of the antifungal agents currently available. In recent decades, many experimental and clinical studies have shown fluconazole to be effective against deep keratitis (Al-Hussaini et al 1994;Goldblum et al 2005).…”

Penetration of Topically Administered 0.5-Percent Caspofungin Eye Drops into Human Aqueous Humor

“…Caspofungin eye drops are effective for treatment of fungal keratitis in rabbits (11,18) and have good penetration into animal eyes with inflammation or previous corneal abrasion (10,23). Clinically, caspofungin is administered mostly intravenously (1,4,6,9,19,20) or intravitreally (24) for ocular mycosis.…”

“…Caspofungin eye drops (0.5%) (11,13,22) were prepared aseptically; 10.5 ml of water for injection was added to a 50-mg vial of caspofungin. All eye drops were freshly prepared and used within 24 h (7).…”

Rapid and Sensitive Liquid Chromatography/Mass Spectrometry Assay for Caspofungin in Human Aqueous Humor

“…Accordingly, it is important to investigate the topical application of newer antifungal agents that are available only as injections. In rabbit models (5,8), caspofungin eye drops were effective in inhibiting the progression of fungal keratitis. It remains unknown if caspofungin eye drops are able to penetrate the human eye.…”