Page 1114 - Clinical Small Animal Internal Medicine

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1052 Section 9 Infectious Disease

potency of voriconazole against veterinary fungal iso glucan, an essential component of the cell wall in certain
VetBooks.ir lates appears to be favorable when compared to itracona fungi. In susceptible fungi, the integrity of the cell wall is
compromised, leading to cell lysis.
zole. Voriconazole is available as an oral tablet or
The clinical use of the echinocandins is limited
solution, or as an IV preparation. The use of voricona
zole has been reported in cats with unilateral orbital to Candida and Aspergillus spp. in human patients;
aspergillosis; however, it has also been reported to cause Cryptococcus neoformans and the zygomycetes are typi
neurologic deficits in cats, including ataxia, hindlimb cally resistant. The mycelial forms of Blastomyces
paralysis, and visual abnormalities. dermatitidis and Histoplasma capsulatum appear to be
Posaconazole is a lipophilic second‐generation triazole susceptible to the echinocandins, although the yeast
derived from itraconazole. It was approved for use in forms are not, due to the predominance of alpha‐glucan,
people for prophylaxis of invasive Aspergillus and which is not a target of echinocandins, in the yeast cell
Candida infections and for treatment of oropharyngeal wall. Echinocandins have poor oral bioavailability and
candidiasis. Posaconazole also appears to have efficacy are only available in intravenous formulations. The side‐
against Blastomyces, Histoplasma, and Coccidioides spp. effects associated with echinocandins are typically mini
As with itraconazole, administration of posaconazole mal, with fever, gastrointestinal signs, phlebitis, and
with a meal appears to improve bioavailability; however, headache being most commonly reported.
like fluconazole, alterations in gastric acidity do not
appear to affect posaconazole absorption.
The most common adverse effects reported in human Terbinafine
patients are headache and gastrointestinal upset; hepa
totoxicity and QT interval prolongation are reported Terbinafine belongs to the allylamine group of antifungal
but much less common. Although posaconazole appears agents, and is most frequently used in people for the
to have a narrower drug interaction profile, inhibition treatment of dermatophytoses and toenail onychomyco
of CYP3A4 has been demonstrated in humans. sis. Its antifungal activity is mediated via noncompetitive
Posaconazole is available only in oral formulations. inhibition of squalene epoxidase, an enzyme involved in
fungal ergosterol synthesis, with more than 4000‐fold
Topical Azoles selectivity for fungal versus mammalian P450 enzymes.
Terbinafine is very well absorbed from the gastrointesti
Both clotrimazole and enilconazole are classified as imi nal tract and then rapidly diffuses from the bloodstream
dazoles within the azole class of drugs; however, both into the dermis and epidermis. Terbinafine is highly
drugs have minimal systemic bioavailability due to a high lipophilic, which leads to its high concentration in hair
first‐pass effect. These drugs are thus confined to topical follicles, skin, nail plate, and adipose tissue, with levels in
use, such as clotrimazole in otic suspensions for the the stratum corneum exceeding those in plasma by a fac
treatment of Malassezia otitis in dogs and cats. Both tor of 75 within 12 days of therapy.
clotrimazole and enilconazole are effective, when Terbinafine has shown high in vitro efficacy against
instilled into the nasal passages, for treating sinonasal many dermatophytes, including Trichophyton and Tinea
aspergillosis in dogs; clotrimazole has also been reported spp. It has also been combined with echinocandins or
to be effective in cats with nasal aspergillosis. Although triazoles in a multimodal approach to systemic mycoses
some dogs require multiple treatments, more than 85% in people. Side‐effects are generally limited to gastroin
of dogs can be cured with up to three treatments. testinal upset and, rarely, hepatotoxicity. Terbinafine is
currently available in tablet form as well as a topical
cream or gel.
Echinocandins In dogs, terbinafine has in vitro activity against
Microsporum and Trichophyton isolates, with little
Echinocandins are a relatively new class of antifungal evidence of acquired resistance during treatment.
medications; the first compound, caspofungin, was Terbinafine appears to be equivalent or superior to keto
approved by the FDA in 2001. Echinocandins inhibit conazole for the treatment of Malassezia dermatitis in
glucan synthase and prevent the synthesis of beta‐1,3 dogs, with a reduction in both yeast counts and pruritus.