Keratomycosis in five dogs

Five cases of canine keratomycosis were diagnosed and treated at a private Veterinary Ophthalmology Practice in Melbourne, Australia. Clinical presentations varied between dogs. Predisposing factors were identified in 4 of 5 cases. Diagnostic modalities utilized were corneal cytology and fungal culture. Corneal cytology confirmed the presence of fungal organisms in all five cases. Aspergillus, Scedosporium, and Candida were cultured from three cases, respectively. Specific antifungal treatment included 1% voriconazole solution or 1% itraconazole ointment. Keratectomy and conjunctival grafting surgery was performed in two patients. Resolution of infection and preservation of vision were achieved in 4 of 5 patients.     

Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration

Aspergillosis is a condition causing serious morbidity and mortality in captive penguins and other bird species. It can be treated with antifungal drugs, such as voriconazole. However, the pharmacokinetics of voriconazole are variable between different animal and bird species. Therefore, the pharmacokinetics of voriconazole were investigated in this study in Magellanic penguins. Pharmacokinetic models were constructed and applied to predict the pharmacokinetics of voriconazole during long‐term treatment in Magellanic penguins, since the voriconazole treatment duration in chronic aspergillosis cases can last up to several months. Plasma voriconazole concentration–time data from adult Magellanic penguins (Spheniscus magellanicus; n = 15) following a single oral (PO) dose of either 2.5 mg/kg or 5 mg/kg in a herring in three separate study periods 7–12 months apart were collected. Mean plasma voriconazole concentrations were above the targeted MIC for Aspergillus fumigatus for 2 hr following a single 2.5 mg/kg voriconazole dose while the plasma concentrations exceeded the MIC for least 24 hr following a 5 mg/kg dose. Nonlinear mixed‐effects modeling was used to fit two pharmacokinetic models, one with first‐order and another with saturable elimination, to the single‐dose data. Fits were good for both, as long as dose was included as a covariate for the first‐order model so that clearance was lower and the half‐life longer for animals receiving the 5 mg/kg dose. Although the single‐dose data suggested saturated elimination at higher concentrations, the model with saturable elimination did not predict plasma voriconazole concentrations well for a clinical aspergillosis case receiving long‐term treatment, possibly because of induction of metabolizing enzymes with chronic exposure. Pharmacokinetic models should accurately predict plasma drug concentrations for different dosage regimens in order to be applicable in the field. Future studies should focus on determining clearance at steady‐state to be able to refine the pharmacokinetic models presented here and improve model performance for long‐term oral voriconazole administration in Magellanic penguins.     

Aspergillus flavus keratomycosis in a cat treated with topical 1% voriconazole solution

An 8-year-old male castrated Domestic Short-haired cat was examined for a 1-week history of blepharospasm and mucoid ocular discharge OS. Examination revealed ulcerative keratitis with stromal loss, stromal infiltrate, corneal edema, perilimbal vascularization and miosis. Cytology of the cornea revealed multiple dichotomously branching, septate fungal hyphae and severe, predominantly neutrophilic inflammation. PCR of the cytology samples confirmed the presence of Aspergillus flavus while fungal and bacterial cultures were negative. Treatment with topical 1% voriconazole solution was successful in resolving the keratomycosis.     

Subconjunctival voriconazole for the treatment of mycotic keratitis in a horse

Fungal keratitis in the horse is a common but challenging disease. This report describes the successful treatment of Fusarium keratitis with both topical and subconjunctival voriconazole 1%. Voriconazole is a new triazole antifungal that has demonstrated efficacy against common fungal pathogens. Topical voriconazole is able to penetrate the intact corneal epithelium making it a good choice for superficial or deep mycotic keratitis. Reports of subconjunctival use of antifungal drugs are sparse in the veterinary literature. We found subconjunctival voriconazole was well tolerated and easy to safely administer.     

CASE REPORT: Keratomycosis in a dog treated with topical 1% voriconazole solution

A 2‐year‐old Jack Russell Terrier was presented for treatment of a worsening corneal ulcer and keratomalacia following removal of a vegetative foreign body. The keratomalacia responded to topical gentamicin therapy; however, the eye became suddenly painful and at examination two areas of increased opacity had developed. Fungal keratitis was demonstrated by corneal scrape showing branching, septate fungal hyphae. Treatment with 1% voriconazole was effective in resolving the keratomycosis.     

Therapy of systemic fungal infections: a pharmacologic perspective

An increase in the incidence of severe, invasive, systemic fungal infections has been noted over the last decade in human and veterinary medicine. Reports of drug resistance and therapeutic failure to currently available antifungal agents have also been on the rise. Many factors are likely to be involved in these trends, including immune suppression and the use of broad-spectrum antibiotics. The use of fungistatic drugs, suboptimal doses, compounded drugs, poorly absorbed drug formulations, and inadequate tissue penetrations of antifungals also contribute to the development of acquired resistance. Because of the unique chemical complexities of the antifungal agents, drug/drug and drug/food interactions may also play a significant role in poor therapeutic outcome. This review summarizes the pharmacology and toxicology of the antifungal agents in current use for systemic mycosis and introduces some of the newer antifungal agents that anecdotally show very promising results.