Blastomycosis Medication

Choice of medication used to treat blastomycosis should be based on type, extent, and severity of disease; the immune status of the patient; and the toxicity of the drug.

Amphotericin B and itraconazole continue to be the main drugs of choice.

Patients with life-threatening disease, pulmonary (eg, ARDS) or extrapulmonary, should be treated with amphotericin B at a high dose of 0.7-1 mg/kg/d to a total dose of 1.5-2 g. However, amphotericin is associated with several toxic effects, most notably renal impairment. Infusion of saline before, during, and after amphotericin reduces renal toxicity. Other effects include thrombophlebitis at the injection site, chills, fever, nausea, hypokalemia, and anemia. Lipid formulation of amphotericin (daily intravenous at 3-5 mg) is less likely to cause renal impairment and may be a better alternative in patients with CNS infection. In patients with moderately severe to severe pulmonary disease or disseminated disease, amphotericin B is the recommended drug and in most cases the dosage recommended is the same as in life-threatening disease.^[12]

It is reasonable to consider switching to itraconazole after clinical improvement. Although not well studied, current expert opinion is to treat with itraconazole 200 mg 3 times daily for 3 days, then twice daily for 6 months. It is recommended to check the serum itraconazole level 2 weeks into treatment to ensure the level is appropriate.

Itraconazole is the drug of choice in mild-to-moderate pulmonary blastomycosis. The appropriate dose is 200 mg/d for 6 months. The value of a higher dose is uncertain. Gastric acidity is required for absorption of itraconazole. Itraconazole provides the ease of oral administration, low toxicity, and high efficacy. Other azoles (eg, ketoconazole, fluconazole) at 400-800 mg/d for 6 months are less desirable alternatives. Itraconazole is absorbed better, has less toxicity, and has stronger antifungal effect than ketoconazole. If disease progresses while on any azole, therapy should be changed to amphotericin B. Azoles are contraindicated in pregnancy.

Patients with CNS blastomycosis should be treated with amphotericin B (dose schedule as in life-threatening disease). Ketoconazole and itraconazole are not appropriate drugs for CNS disease. Fluconazole has good cerebrospinal fluid penetration and the dose recommended is a minimum of 800 mg/d. Voriconazole, a newer antifungal agent, has been successfully used in immunocompromised patients and in those with CNS infection. Voriconazole has good cerebrospinal fluid penetration.^{[13, 14]}

Patients with mild-to-moderate disseminated blastomycosis without CNS involvement should be treated with itraconazole 200-400 mg/d for 6 months. Treatment period should be extended to 12 months in patients with bone involvement (osteomyelitis).

Immunocompromised patients should be treated early and aggressively with amphotericin B as in life-threatening disease. After the amphotericin B course, chronic suppressive therapy with itraconazole may be needed in some cases.

Clinical data on using newer drugs (ie, posaconazole, caspofungin, micafungin) for the treatment of blastomycosis are insufficient.

Class Summary

Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Amphotericin B deoxycholate (AmBisome)

Alters fungal cell membrane permeability by binding with ergosterol, resulting in cell component leakage and death.

Administered IV and must be mixed with dextrose in water.

Itraconazole (Sporanox)

Synthetic thiazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450-dependent synthesis of ergosterol, a vital component of fungal cell membranes.