A 56-year-old woman comes to the emergency department due to 1 day of fever. She has a history of a hematologic malignancy and recently completed a cycle of chemotherapy through an indwelling central venous catheter. Temperature is 38.3 C (100.9 F). Laboratory studies are notable for neutropenia, with an absolute neutrophil count of 380/mm³. The patient is started on broad-spectrum antibiotics. Three days later, she continues to be febrile. Fungal cultures grow a species of Candida with a mutation in a gene coding an enzyme responsible for synthesizing a fungal cell wall polysaccharide. The organism is most likely to be resistant to which of the following antifungal agents as a result of this mutation?

Question

Quizplus · Accepted Answer

11ec160b_380c_3c32_9249_99bd05076e63_MD0001_00 A major polysaccharide component of the fungal cell wall is 1,3-beta-D-glucan. Caspofungin and the other echinocandin antifungals (eg, micafungin) block glucan synthesis. Whereas polyene and azole antifungals target the fungal cell membrane, the echinocandins are unique in that they suppress fungal cell wall synthesis. Caspofungin is most active against Candida species and Aspergillus. It is not active against Cryptococcus neoformans and has limited activity against Mucor and Rhizopus species. This patient likely has an infection due to a caspofungin-resistant strain of Candida (uncommon). (Choice A) Amphotericin B is a polyene antifungal that binds ergosterol in the fungal cell membrane and leads to pore formation and cell lysis. (Choice C) Flucytosine inhibits the synthesis of both DNA (replication) and RNA (protein synthesis) in fungal cells. It is mainly used as a synergistic agent with amphotericin B, particularly in the treatment of cryptococcal meningitis. (Choice D) Griseofulvin enters fungal cells, binds microtubules, and inhibits mitosis. This antifungal drug is effective only against dermatophyte fungi as it accumulates in keratin-containing tissues. (Choice E) Itraconazole is an azole antifungal that inhibits ergosterol synthesis. It does not affect the polysaccharides of the fungal cell wall. (Choice F) Terbinafine accumulates in skin and nails and is used to treat dermatophytosis. Terbinafine inhibits the fungal enzyme squalene epoxidase, which ultimately results in decreased ergosterol synthesis. Educational objective: Echinocandins (eg, caspofungin, micafungin) are antifungal medications that inhibit synthesis of the polysaccharide glucan, an essential component of the fungal cell wall.

A 56-Year-Old Woman Comes to the Emergency Department Due to 1