A 43-year-old man comes to the emergency department due to fever, chest pain, and hemoptysis. He has a history of a hematologic malignancy for which he recently underwent a cycle of chemotherapy. Laboratory studies show neutropenia due to the chemotherapeutic agents. A nodule with surrounding hypoattenuation is revealed on chest CT. Galactomannan and beta-D-glucan assays are elevated. Sputum cultures grow Aspergillus. The patient is placed on intravenous amphotericin B. During the infusion, he develops headaches, rigors, and hypotension. Over the next few days, there is a decline in renal function attributed to amphotericin. These toxic effects are likely due to binding of the antifungal agent to which of the following?

Question

A 43-year-old man comes to the emergency department due to fever, chest pain, and hemoptysis.  He has a history of a hematologic malignancy for which he recently underwent a cycle of chemotherapy.  Laboratory studies show neutropenia due to the chemotherapeutic agents.  A nodule with surrounding hypoattenuation is revealed on chest CT.  Galactomannan and beta-D-glucan assays are elevated.  Sputum cultures grow Aspergillus.  The patient is placed on intravenous amphotericin B.  During the infusion, he develops headaches, rigors, and hypotension.  Over the next few days, there is a decline in renal function attributed to amphotericin.  These toxic effects are likely due to binding of the antifungal agent to which of the following?

Quizplus · Accepted Answer

This patient with febrile neutropenia following chemotherapy has invasive aspergillosis (fever, chest pain, hemoptysis, chest imaging showing nodule with hypoattenuation consistent with "halo sign"). Amphotericin B is a mainstay of treatment for many systemic mycoses. It preferentially binds the ergosterol of fungal cell membranes, leading to fungal cell lysis. This drug is relatively selective as it has a higher affinity for ergosterol (in fungal membranes) than for cholesterol (in human cell membranes). However, it binds cholesterol to a degree, which explains a large number of its adverse effects. Amphotericin B is often administered intravenously. Its main toxicities include the following: (Choice B) Triazole antifungals (eg, fluconazole, itraconazole) inhibit cytochrome P450 enzymes, suppressing the metabolism of many other medications. This effect explains the myriad drug interactions of this group of antifungal agents. (Choice C) Binding of microtubular proteins is the mechanism of griseofulvin, which is effective against dermatophytes only. (Choices D and E) Amphotericin B does not interact with ribosomal subunits or mitochondrial enzymes. Educational objective: Amphotericin B binds the ergosterol of fungal cell membranes to exert its antifungal effects. However, it also binds cholesterol to some degree, causing toxicity to human tissues. The most important adverse effects of amphotericin B are nephrotoxicity, hypokalemia, and hypomagnesemia.

A 43-Year-Old Man Comes to the Emergency Department Due to Fever