Successful Treatment of Fusarium Endophthalmitis With Voriconazole and Aspergillus Endophthalmitis With Voriconazole Plus Caspofungin

Durand, Marlene L.; Kim, Ivana K.; D’Amico, Donald J.; Loewenstein, John I.; Tobin, Ellis; Kieval, Shalom J; Martin, Stephen S.; Azar, Dimitri T.; Miller, Frederick S.; Lujan, Brandon J.; Miller, Joan W.

doi:10.1016/j.ajo.2005.03.030

Cited by 84 publications

(36 citation statements)

References 7 publications

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“…The same drug combination has been used to successfully treat a patient with endophthalmitis due to Aspergillus fumigatus [6]. Clinical reports on the utility of caspofungin monotherapy for ocular infections are scarce and conflicting.…”

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confidence: 99%

Ocular penetration of caspofungin in a rabbit uveitis model

Goldblum

Fausch

Frueh

et al. 2006

Graefe's Arch Clin Exp Ophthalmol

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Background Little is known about the ocular penetration of echinocandin antifungals. We studied the ocular distribution of systemically administered caspofungin in a rabbit uveitis model. Methods Caspofungin (1 mg/kg per day) was given intravenously to rabbits as a single dose or as repeated daily doses on 7 days starting 24 h after induction of unilateral uveitis by intravitreal endotoxin injection. Caspofungin concentrations were determined by high-performance liquid chromatography in the cornea, aqueous humor, vitreous humor, and serum 4, 8, 16, and 24 h after administration of a single dose and 24 h after the last of seven doses. Results The mean caspofungin concentration in the aqueous of the inflamed eye 4 and 8 h after single-dose administration was 1.30 ± 0.39 μg/ml and 1.12 ± 0.34 μg/ml, respectively. Drug concentrations decreased to 0.24±0.09 μg/ml at 16 h and 0.26±0.14 μg/ml at 24 h. In the vitreous of inflamed eyes drug levels were undetectable at all time points. No drug was found in the aqueous of inflamed eyes 24 h after the last of seven repeated doses, and the vitreous only contained trace amounts. In the corneas of inflamed eyes concentrations reached 1.64±0.48 μg/g at 4 h, peaked at 2.16±1.14 μg/g at 8 h, and declined to 1.87±0.52 μg/g and 1.49±0.48 μg/g at 16 and 24 h, respectively. After repeated dosing, corneal concentrations of caspofungin were 0.8 and 1.0 μg/g and below the limit of detection in two of four animals. In noninflamed eyes no drug was detectable in the aqueous and vitreous humor, and the corneas at any time point. Conclusions In our model, caspofungin reached therapeutically relevant levels in the aqueous and cornea but not in the vitreous humor of inflamed eyes. Intraocular drug deposition was critically dependent on a disrupted bloodeye barrier. These findings suggest a limited role for caspofungin in the treatment of fungal endophthalmitis.

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Ocular penetration of caspofungin in a rabbit uveitis model

Goldblum

Fausch

Frueh

et al. 2006

Graefe's Arch Clin Exp Ophthalmol

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“…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. The successful use of topical caspofungin alone (13) or in combination with voriconazole (22) has been reported for two patients.…”

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confidence: 99%

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

Neoh

Leung

Misra

et al. 2011

Antimicrob Agents Chemother

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Ten participants attending elective anterior segment eye surgery received 0.5% caspofungin eye drops either 1 drop hourly for 4 h or 1 drop an hour before surgery. The eye drops were generally well tolerated. In the absence of inflammation or corneal abrasion, topical caspofungin does not achieve clinically relevant concentrations.Fungal keratitis is a potentially blinding condition, with Candida, Aspergillus, and Fusarium spp. (2, 21) being the common pathogens. Current treatment for fungal keratitis is inadequate (8); thus, alternatives are needed.Caspofungin has activity against a wide range of fungi, with MIC 90 values ranging from 60 to 2,000 ng/ml (15, 23). 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. The successful use of topical caspofungin alone (13) or in combination with voriconazole (22) has been reported for two patients. However, the utility of topical caspofungin in fungal keratitis remains unknown, partly due to limited data on its penetration into human aqueous humor after topical administration. This study aimed to investigate the ocular penetration of 0.5% caspofungin eye drops into human aqueous humor.

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“…Voriconazole has the broadest antifungal spectrum of azole antifungal agents [2,20] and it is effective against Fusarium when used in vivo [17]. There are case reports about the improvement of F.solani keratitis [2,10] or corneal abscess [16] with topical and systemic voriconazole together, whereas Durand et al [6] reported improvement in F. moniliforme endophthalmitis with systemic voriconazole alone. There is not a suggested concentration and application frequency of topical voriconazole, and the concentrations used change from 0.1% to 2% whereas the application frequency changes from every half hour to 7 times per day.…”

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confidence: 94%