A number of agents that have antifungal activity are applied topically, either on the skin, in the ear or eye, or on mucous membranes (buccal, nasal, vaginal) to control superficial mycotic infections. Concurrent systemic treatment with griseofulvin is often helpful for therapeutic management of dermatophyte infections. The hair should be clipped from affected areas and the nails trimmed to fully expose the lesions before antifungal preparations are applied. Bathing the animal may also be helpful. Isolation or restricted movement of infected animals is wise, especially when dealing with zoonotic fungi.
Preparations may be administered in the form of solutions, lotions, sprays, powders, creams, or ointments for dermal application, or in the form of irrigant solutions, ointments, tablets, or suppositories for intravaginal use. The concentration of active principle in these preparations varies and depends on the activity of the specific agent.
The clinical response to local antifungal agents is unpredictable. Resistance to many of the available drugs is common. Spread of infection and reinfection add to the difficulty of controlling superficial infections. Perseverance is often an essential element of treatment.
Some topical antifungal agents that have been administered with success in various conditions and species include iodine preparations (tincture of iodine, potassium iodide, iodophors), copper preparations (copper sulfate, copper naphthenate, cuprimyxin), sulfur preparations (monosulfiram, benzoyl disulfide), phenols (phenol, thymol), fatty acids and salts (propionates, undecylenates), organic acids (benzoic acid, salicylic acids), dyes (crystal [gentian] violet, carbolfuchsin), hydroxyquinolines (iodochlorhydroxyquin), nitrofurans (nitrofurazone, nitrofurfurylmethyl ether), azoles (miconazole, tioconazole, clotrimazole, econazole, thiabendazole), polyene antimicrobials (amphotericin B, nystatin, pimaricin, candicidin, hachimycin), allylamines (naftifine, terbinafine), thiocarbamates (tolnaftate), and miscellaneous agents (acrisorcin, haloprogin, ciclopirox, olamine, dichlorophen, hexetidine, chlorphenesin, triacetin, polynoxylin).
A scant proportion (2%–3%) of clinical mastitis cases in cattle are of myotic origin with most cases due to Candida; Cryptococcus and Trichosporon have also been implicated. Historically, mycotic mastitis has been treated via frequent stripping of the affected quarter; however, successful treatment outcomes with intra-arterial and intramammary injection of miconazole have also been described.
Respiratory Therapy
In small animals and equine patients, systemic antifungals are typically administered in the management of fungal pneumonia. However, the treatment and delivery of antifungals in affected poultry remains a challenge. In avian species, pulmonary aspergillosis is a significant cause of morbidity and mortality in affected flocks, and domestic poultry and ornamental and wild birds are all susceptible. While environmental management and antimycotic disinfectants can play a role in mitigating disease spread in flocks, treatment is generally unrewarding, and there are no FDA-approved treatments for fungal pneumonia. Keeping that in mind, due to the lipophilic nature and the persistent tissue half-life of the majority of these drugs, an extremely extended egg and meat withdrawal time should be anticipated for any extra-label use of antifungals in poultry.
Direct administration of antifungals to the upper respiratory tract is becoming more common in avian species. Both intratracheal administration or nebulization of amphotericin B or clotrimazole and miconazole have been described in the literature for the treatment of poultry aspergillosis. Typically, nebulization or intratracheal administration is performed in combination with systemic antifungal treatment, such as itraconazole.
Instillation of antifungals directly into the nasal cavity is a common treatment for fungal rhinitis in dogs, cats, and horses. Nasal aspergillosis most commonly affects dogs, while C neoformans most commonly affects cats. Nasal disease in dogs and cats may also be due to Trichosporon, Blastomyces, and Histoplasma. Nasal aspergillosis has been reported in horses, and guttural pouch mycosis is most frequently due to Aspergillus spp.
Dosages of Antifungals for Respiratory Therapy
Drug | Dose, Route, Frequency, Species |
|---|---|
Amphotericin B | Nebulization: 1 mg/mL solution in sterile water or saline for 15 minutes, q 6–12 h (avian) Intratracheal: 1 mg/kg, q 8–12 h (avian) |
Clotrimazole | Nebulization: 1% aqueous solution for 30 minutes, q 24 h (avian) Intratracheal or direct air sac administration: 10 mg/kg (avian) Intranasal: Instill into nasal cavity under general anesthesia for 1 hour, rotating head q 15 min (dogs) |
Miconazole | 45 minutes/day (avian) Intranasal: 2% miconazole (horses) |
Enilconazole | Intranasal: 5% solution, instillation under general anesthesia for 1 hour, rotating head q 15 min (dogs) Topical: Instill twice daily via nasal or guttural pouch catheter, q 12 h (horses) |
Terbinafine | Nebulization: 1 mg/mL in aqueous solution for 20 minutes, q 8 h (avian) |
Aural Therapy
Fungal organisms can be both primary (Aspergillus) and secondary (yeast) causes of otitis externa in small animals. Yeast (Malassezia, Candida) is the most common cause of otitis externa in dogs, and there are a number of FDA-approved products for the treatment of otitis externa. Most cases of otitis externa respond favorably to topical treatment; however, severe refractory cases may require systemic antifungals such as terbinafine, fluconazole, itraconazole, or ketoconazole. A large number of FDA-approved topical antifungal products are approved for otitis externa. Effective multiple-dose antifungals include clotrimazole, miconazole, thiabendazole, acetic acid, and TrizEDTA and ketoconazole flush. Two newer single-dose formulations containing terbinafine are also FDA approved with effects lasting 30 days post-administration.
Ocular Therapy
Depending on the geographic area, keratomycosis can be a common ophthalmic condition in horses, dogs, and cats. Fungal culture is recommended in cases of keratomycosis because the fungal species and antifungal sensitivity patterns vary greatly by geographic region. Miconazole, natamycin, fluconazole, econazole, voriconazole, clotrimazole, and itraconazole have been successfully administered topically to treat fungal ulcers in horses.
Topical Therapies for Keratomycosis
Drug | Concentration | Frequency | Notes |
|---|---|---|---|
Fluconazole | 0.2% solution | q 2–6 h | Subconjunctival and intravitreal injections have been described |
Itraconazole | 1% ointment/30% DMSO | q 2–6 h | Does not penetrate anterior chamber |
Miconazole | 1% solution | q 2–6 h | Subconjunctival and intracameral injections have also been described |
Voriconazole | 1% solution | q 2–6 h | Penetrates intact corneal epithelium |
Amphotericin B | 0.075%–5% solution | q 2–6 h | Subconjunctival, intravitreal, and intracameral injections after proper dilution have also been described |
Natamycin | 5% suspension | q 2–6 h | Only FDA-approved drug for fungal keratitis (humans); does not penetrate intact corneal epithelium |
Terbinafine | 1% ointment | q 2–6 h | Not suitable for deep corneal or intraocular mycoses |
Silver Sulfadiazine | 1% ointment/cream | q 6–24 h |
Ophthalmic use of the azole class in the treatment of keratomycosis and other fungal diseases is common. Ophthalmic formulations of the azoles are not commercially available; however, success has been reported after the use of compounded miconazole (1% solution) and itraconazole. Combining itraconazole with 30% dimethyl sulfoxide (DMSO) in the compounding process increases corneal drug concentrations. However, even when combined with DMSO, itraconazole does not penetrate the anterior chamber. The intravenous formulation of voriconazole has been administered in the treatment of keratomycosis, and has been shown to penetrate the intact cornea. Due to its ability to penetrate an intact equine cornea, voriconazole has become a first-line therapeutic choice for equine keratomycosis, as Fusarium, Aspergillus, and Candida are typically susceptible.
Recently, the use of systemic voriconazole at 4 mg/kg/day in horses was reported to reach concentrations above the AUC:MIC ratio of Aspergillus in tear film. A table of commonly used topical antifungal agents is provided below. Topical administration of the allylamine terbinafine has not resulted in detectable aqueous humor concentrations, and therefore its use for deep corneal or intraocular mycosis is not recommended. However, topical use of terbinafine in superficial Aspergillus keratomycosis has been reported to be effective in a rabbit.
