In a severely neutropenic patient with fever, which antifungal is commonly used as initial therapy for suspected invasive fungal infection?

• A. Amphotericin B
• B. Fluconazole
• C. Voriconazole
• D. Caspofungin

Answer: (A)

In severe neutropenia with fever, the risk of an invasive fungal infection is high, so the goal is to start a drug with broad, rapid antifungal activity that covers the common mold and yeast pathogens you’re worried about. Amphotericin B does just that: it binds ergosterol in fungal cell membranes, creates pores, and quickly kills a wide range of fungi, including Candida species and molds like Aspergillus. Because of this broad coverage and the urgency to treat empirically before culture results are available, amphotericin B has long been used as initial therapy in febrile neutropenia when invasive fungal infection is suspected.

Fluconazole, while effective against many yeasts, lacks activity against molds such as Aspergillus, so it isn’t sufficient when invasive mold infection is a concern. Voriconazole has strong mold coverage, including Aspergillus, and is excellent for proven or highly suspected mold infections, but historically it hasn’t been the standard initial empiric choice in all febrile neutropenia protocols. Caspofungin covers Candida well and has activity against Aspergillus, but as a first-line empiric option in high-risk febrile neutropenia, amphotericin B has the broadest initial spectrum.