Voriconazole is preferred over fluconazole for invasive Aspergillus infections. Compared to fluconazole, voriconazole has extended spectrum because it inhibits:

• A Beta-1,3-glucan synthase in Aspergillus cell wall
• B 14-alpha-demethylase in Aspergillus, whereas fluconazole cannot inhibit this enzyme in molds ✓
• C Chitin synthase in Aspergillus hyphal tips
• D Ergosterol peroxidation via generation of reactive oxygen species

Explanation

Both fluconazole and voriconazole inhibit fungal CYP51 (14-alpha-lanosterol demethylase), disrupting ergosterol synthesis. However, voriconazole's pharmacokinetics and its more favorable molecular fit for the CYP51 enzyme of molds (like Aspergillus, Fusarium) give it activity against these organisms which fluconazole lacks. Fluconazole has inadequate penetration and activity against mold CYP51. Echinocandins (caspofungin, micafungin) target beta-1,3-glucan synthase; polyenes (amphotericin B) bind ergosterol directly.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.