A patient on long-term voriconazole therapy for Aspergillus fumigatus infection develops breakthrough infection with a Mucor species. The most important mechanism of intrinsic mucormycetes resistance to voriconazole is:

• A Mucor species lack ergosterol in their cell membranes and use alternative sterols
• B Mucorales express high-level efflux pumps that actively extrude all azoles
• C Mucor CYP51 (lanosterol 14α-demethylase) has structural differences that prevent voriconazole binding with sufficient affinity ✓
• D Voriconazole is metabolized to an inactive compound by Mucor-specific cytochrome enzymes

Explanation

Mucorales (Rhizopus, Mucor, Lichtheimia, Cunninghamella) are intrinsically resistant to voriconazole because their CYP51 enzyme has low affinity for voriconazole due to key amino acid substitutions in the azole-binding domain, unlike Aspergillus or Candida CYP51. They do contain ergosterol. This explains why voriconazole use in immunocompromised patients, particularly those with haematological malignancies, is a risk factor for breakthrough mucormycosis — a phenomenon termed 'ecological niché' selection.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.