First-line treatment for mild to moderate histoplasmosis.

• A. Fluconazole
• B. Voriconazole
• C. Itraconazole
• D. Ketoconazole

Answer: (C)

Itraconazole is the preferred first-line treatment for mild to moderate histoplasmosis because it has strong activity against Histoplasma capsulatum and penetrates tissues well, making it effective for pulmonary and mild disseminated forms. It works by inhibiting the fungal enzyme 14-alpha-demethylase, which blocks ergosterol synthesis and disrupts the fungal cell membrane. The typical regimen starts with 200 mg three times daily for 3 days, then 200 mg twice daily, and is continued for at least 12 months with monitoring of response and liver function. Fluconazole is less potent against Histoplasma and is not preferred as initial therapy; other azoles like voriconazole or ketoconazole have inferior activity or safety concerns, and amphotericin B is reserved for severe disease.