Merck Manual

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Professional Version

Overview of Antifungal Agents for Use in Animals

By

Melissa A. Mercer

, DVM, MS, DACVIM-LA, Virginia Maryland College of Veterinary Medicine

Reviewed/Revised Aug 2022

Pathogenic fungi affecting animals are eukaryotes, generally existing as either filamentous molds (hyphal forms) or intracellular yeasts. In general, most primary fungal infections Overview of Fungal Infections in Animals Systemic mycoses are infections with fungal organisms that exist in the environment, enter the host from a single portal of entry, and disseminate within the host to multiple organ systems.... read more are caused by filamentous fungi, while most opportunistic fungal infections are due to yeasts; however, there is increasing recognition of opportunistic filamentous molds as well. Fungal organisms are characterized by low invasiveness and virulence. Factors that contribute to fungal infection include necrotic tissue, moist environment, and immunosuppression. Fungal infections can be primarily superficial and irritating (eg, dermatophytosis Dermatophilosis in Animals Dermatophilosis is a bacterial skin infection affecting multiple species of animals world-wide. It is most common in young or immunosuppressed animals or in animals chronically exposed to wet... read more Dermatophilosis in Animals ) or systemic and life-threatening (eg, blastomycosis, cryptococcosis, histoplasmosis, coccidioidomycosis). Clinically relevant dimorphic fungi grow as yeastlike forms in a host but as molds in vitro at room temperature; they include Candida spp, Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, Sporothrix schenckii, and Rhinosporidium.

There are five major classes of systemic antifungal agents: polyenes, azoles, allylamines, nucleoside analogs, and echinocandins. Of these classes, polyenes and azoles are most commonly used in veterinary practice. Only a scant number of products are approved for veterinary use in the United States—almost exclusively topical preparations—and therefore the majority of systemic antifungals prescribed are off-label.

Several factors can lead to therapeutic failure or relapse after antifungal treatment. Drug access to fungal targets is often compromised. Host inflammatory response may be the first barrier, followed by location in sanctuaries (brain, eye, etc) as a second barrier for some infections, and the organisms themselves are a third barrier. The fungal cell wall is rigid and contains chitin, which along with polysaccharides, acts as a barrier to drug penetration. The cell membrane contains sterols such as ergosterol, which influences the efficacy of and potential resistance to some drugs. Cryptococcus and occasionally S schenckii produce an external coating or slime layer that encapsulates the cells and causes them to adhere and clump together. Finally, regarding drug access, most infections are located inside host cells, whose lipid membrane can present a final barrier.

Discontinuing treatment after clinical signs have resolved but before infection is eradicated also leads to therapeutic failure. Treatment should extend well beyond the clinical cure. Once drugs reach the site of action, therapeutic success is impeded by the nature of fungal infections. Fungal growth is slow, yet most antifungal drugs work better in rapidly growing organisms. Likewise, most antifungal agents are fungistatic in action, with clearance of infection largely dependent on host response. As such, the duration of treatment is long, and the "get in quick, hit hard, and get out quick" recommendation for antibacterial treatment is not appropriate for antifungal treatment; care must be taken not to discontinue treatment too early.

However, longer duration of treatment contributes to another common cause of therapeutic failure: host toxicity. Because both the antifungal target organism and the host cells are eukaryotic, the cellular targets of fungal organisms are often similar to the host structures. Therefore, as a class, antifungal drugs tend to be more toxic than antibacterial drugs, and the number of antifungal drugs approved for use is markedly lower than the number of antibacterial drugs. Drugs that can be administered locally (including topically) or have better penetration to sites of infection (eg, liposomal products) may decrease this risk. The slow growth that characterizes fungal infections means that acquired resistance occurs less commonly than in bacterial infections. Therapeutic failure may also reflect the inability of the immunocompromised host to overcome residual fungal populations inhibited by the drug; those antifungals that are also (positive) immunomodulators may be more effective.

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