There are a number of classes of antifungal drugs. Research in antifungal drugs has increased dramatically in the last two
decades with the advances in organ transplantation and the epidemic of AIDS. The original antifungal drug was amphotericin
B representing the polyene family. Amphotericin B damages the ergosterol of the fungal cell membrane. The next group of drugs
was the azoles that inhibit the synthesis of the fungal ergosterol in the cell membrane. These are an important group of fungistatic
drugs. Members of this group include ketoconazole, itraconazole, fluconazole as well as newer member such as voriconazole
and posaconazole. The allylamine group interferes with ergosterol production in a different manner than the azoles and is
effective when azole resistance develops. Terbinafine is the representative of the allylamine group. The glucan synthesis
inhibitors interfere with the synthesis of the glucan component of the fungal cell wall thereby providing a different mechanism
of action than the other antifungal drugs. The development of many new drugs for fungal infection is encouraging but the high
cost of many of the new drugs is prohibitive for long term treatment.
Amphotericin B is the oldest of the antifungal drugs and remains the "gold standard." It is effective against a wide range
of fungal organisms and acts in a fungicidal manner damaging the ergosterol of fungal organisms. The damage of the ergosterol
results in leakage of the cell and cell death. The need for intravenous administration and the nephrotoxicity of amphotericin
B limits its usefulness in long term treatment of fungal infections. It is still very effective for initial treatment of fungal
infections because of its rapid action and intravenous route. In dogs with blastomycosis involving the central nervous system
it appears to be superior to itraconazole. In dogs with histoplasmosis of the intestinal tract, malabsorption precludes the
oral administration of azoles. Amphotericin B can be given initially to restore the function of the intestinal tract so that
oral drugs can be used. Short term use of amphotericin B can be done without significant renal damage. It is lifesaving in
these situations. There are a number of new amphotericin B drugs that reduce the renal toxicity by lipid encapsulation of
the drug. This may be especially useful in infections such as histoplasmosis where the encapsulated drug is phagocytosed by
the same macrophages that contain the fungal organisms. This brings drugs and organisms together. The lipid encapsulated drug
is expensive and requires an increased dose of amphotericin B.
To avoid amphotericin B renal toxicity, animals need to be well hydrated before giving the drug. Diuresis does not reduce
renal toxicity in hydrated dogs but administration over a 3 to 4 hour period reduces renal damage. The drug should be given
every 48 hours. BUNs should be done before each dose and drug discontinued as the BUN approaches 50 mg/dl. Starting drug dose
in dogs is 0.5 mg/kg and 0.25 mg/kg in cats. There is minimal data on liposome encapsulated amphotericin B but a suggested
starting dose is 1 mg/kg. Amphotericin B is as effective as intravenously available azoles but is much cheaper.
Ketoconazole is the first of the azole group of antifungal drugs. The newer azoles such as itraconazole and fluconazole are
more effective than ketoconazole and have less toxicity. Ketoconazole frequently produces anorexia in cats. Ketoconazole has
a place in the treatment of Malassezia in dogs and has some antiinflammatory effect in addition to its antifungal activity. Ketoconazole seems to be a fairly good
drug for coccidioidomycosis but fluconazole is probably better.