Systemic antifungal agents: an update of established and new therapies

Terbinafine is the drug of choice for dermatophyte onychomycosis. Adjunct therapies, such as topical agents or surgical approaches, may improve outcomes in patients who have risk factors for incomplete response or recurrence. Despite many studies of newer antifungal agents for tinea capitis, griseofulvin (20 mg/kg/d) remains the gold standard. Terbinafine (> or = 6 mg/kg/d) and fluconazole (8 mg/kg once weekly) have yet to demonstrate comparable efficacy in large-scale RCTs. The current role of second-generation triazoles and echinocandins is for treatment of invasive candidiasis and invasive aspergillosis in patients who are critically ill and immunocompromised. Strengths of the newer triazoles include increased activity against resistant and emerging pathogens, convenience of oral formulations, and in vivo activity against subcutaneous mycoses, in particular eumycotic mycetoma. Their metabolism via cytochrome P450 isoenzymes increases the risk for significant drug interactions, and their established mechanism of action may lead to development of resistant pathogens. The echinocandins inhibit fungal cell wall synthesis, a novel therapeutic target; thus, they are effective against azole-resistant species. Their metabolism is independent of hepatic cytochrome P450 enzymes, minimizing drug interactions. They are available only as i.v. formulations.