- Author: Chidinma Chima-Okereke, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP more...
Medication for the treatment of blastomycosis should be selected on the basis of the 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.
Alternative antifungals include ketoconazole, fluconazole, and voriconazole. Fluconazole and voriconazole have good cerebrospinal fluid penetration. Voriconazole has been successfully used in immunocompromised patients and in those with central nervous system (CNS) infection.
The mechanism of action of antifungal agents 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
Amphotericin B is the initial drug of choice for blastomycosis in patients with severe illness (eg, rapidly progressive infections, CNS disease), immunocompromised hosts, and special circumstances (eg, pregnant women, children). This agent alters fungal cell membrane permeability by binding with ergosterol, resulting in cell component leakage and death.
Amphotericin B is administered intravenously and must be mixed with dextrose in water. Infusion of saline before, during, and after amphotericin reduces renal toxicity.
The 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 and pregnant women.
Itraconazole is a 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. Compared with other oral azoles, itraconazole is better absorbed and has enhanced antimycotic activity with fewer adverse effects.
Oral itraconazole (at a dosage of 200-400 mg/d) is the azole of choice in adult patients with indolent nonmeningeal blastomycosis of mild-to-moderate severity. It may be given as primary therapy to stable patients or as step-down therapy following a course of amphotericin B.
Ketoconazole is an effective alternative agent in the treatment of immunocompetent patients with mild-to-moderate blastomycosis. High rates of serious adverse effects and of relapse limit its usefulness.
Fluconazole is a highly selective inhibitor of the fungal cytochrome P-450–dependent enzyme lanosterol 14-alpha-demethylase. Subsequent loss of normal sterols correlates with accumulation of 14 alpha-methyl sterols in fungi and may be responsible for the fungistatic activity of fluconazole. It has a limited role in the treatment of blastomycosis; however, it can be used as step-down therapy in CNS blastomycosis due to its excellent nervous system penetration.
A triazole antifungal agent, voriconazole acts by inhibition of fungal cytochrome P-450 and sterol C-14 alpha-demethylation. Voriconazole has good cerebrospinal fluid penetration and has been recommended for step-down therapy from amphotericin B in patients with CNS blastomycosis.
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