Imidazoles and triazoles function by inhibiting fungal cytochrome P-450–dependent enzymes, thereby blocking synthesis of the fungal cell membrane. The triazoles (fluconazole, itraconazole) offer a less-toxic alternative to amphotericin B for the treatment of cryptococcal meningitis and other invasive fungal diseases, and they may also play a role in the long-term suppression of Cryptococcus after remission of acute infection in severely immunocompromised patients. Ketoconazole is often less effective than the newer triazoles and carries a higher risk of hepatotoxicity. Voriconazole, a second-generation triazole, is available in both intravenous and oral formulations. It offers a better treatment option for invasive aspergillosis and other serious fungal infections. For more on antifungal agents, see Table 14-3.
Treatment of serious, deep-seated, systemic fungal infections may require the use of intravenous amphotericin B, sometimes in combination with either flucytosine or a triazole. Lipid complex and liposome-encapsulated formulations of amphotericin B are available to reduce the drug’s toxicity. Nystatin, which is structurally similar to amphotericin B, is an antifungal agent administered topically, vaginally, or by mouth. Terbinafine, an allylamine oral antifungal agent, and butenafine, a benzylamine, are effective in controlling onychomycosis due to chronic dermatophyte infections.
Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1–50.
Zonios D, Yamazaki H, Murayama N, et al. Voriconazole metabolism, toxicity, and the effect of cytochrome P450 2C19 genotype. J Infect Dis. 2014;209(12):1941–1948.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.