Empiric antifungal therapy is rarely instituted except for immunocompromised (eg, febrile neutropenia) and other high-risk patients. Therapy generally is reserved for situations in which yeast or mold is seen on KOH preparation test or when isolated organisms are thought to be pathogenic. Antifungal standardized susceptibility testing is available for Candida spp and predicts clinical outcome. In contrast, susceptibility testing for most other fungi is only available at certain centers; in vitro results for these pathogens are less predictive of patient outcomes due to limited clinical experience.
Amphotericin B is a broad-spectrum agent active against Aspergillus, Histoplasma, Cryptococcus, Coccidioides, Candida, Blastomyces, Sporothrix, Mucor, among others. Pseudallescheria boydii and Fusarium are often resistant to amphotericin B.
LIPID-BASED AMPHOTERICIN B
The nephrotoxicity of conventional amphotericin has resulted in the development of lipid-based amphotericin B products. The most commonly used agent is liposomal amphotericin B (L-AmB; AmBisome). Liposomal amphotericin B 10 mg/kg/day is no better, but more nephrotoxic, than 3 mg/kg/day in the treatment of invasive mold infection. The most common dose in the treatment of invasive aspergillosis is 5 mg/kg daily. Liposomal amphotericin B is effective in the treatment of visceral leishmaniasis. Short courses (5–10 days) with low doses (2–4 mg/kg/day depending on which preparation is used) are very effective in eradicating the parasite, probably because of distribution of the medication to the reticuloendothelial system, the major site of parasite invasion.
Liposomal amphotericin B is associated with less nephrotoxicity and infusion reactions when compared with conventional amphotericin B.
CONVENTIONAL AMPHOTERICIN B
The availability of lipid-based amphotericin, echinocandins, and triazoles has resulted in a greatly reduced role for conventional amphotericin for the prevention and treatment of fungal infection. If conventional amphotericin B is used, the daily dose for most fungal infections varies from 0.3 mg/kg to 0.7 mg/kg, although infections caused by Aspergillus and Mucor are often treated with 1–1.5 mg/kg daily.
Electrolyte disturbances (hypokalemia, hypomagnesemia, distal renal tubular acidosis) also commonly occur. Kidney injury can be reduced with sodium supplementation and intravenous hydration.
Nystatin has a wide spectrum of antifungal activity but is used almost exclusively to treat superficial candidal infections. It is too toxic for systemic administration, and the medication is not absorbed from mucous membranes or the gastrointestinal tract. Several preparations are available, including oral suspension (100,000 units/mL) and ointments, gels, and creams (100,000 units/g). For oral candidiasis, 500,000 units of suspension are used as a “swish and swallow” and repeated four times a day for at least 2 days after resolution of the infection. Infections of skin are treated with cream or ointment with 100,000 units applied to the affected area twice daily until resolution of the infection.
Flucytosine inhibits some strains ...