A patient with haematological malignancy on prolonged antifungal prophylaxis with voriconazole develops a pulmonary infection. CT shows a halo sign followed by air-crescent sign on follow-up. BAL galactomannan is elevated. Biopsy shows septate hyphae branching at acute angles (45°). Treatment is initiated with voriconazole, but the fungus tests resistant. The most likely organism and resistance mechanism is:
- A Mucor species; intrinsic resistance to voriconazole via cell wall composition
- B Fusarium species; resistance via overexpression of efflux pumps
- C Aspergillus fumigatus; acquired resistance via cyp51A mutations in the azole target (lanosterol 14α-demethylase) ✓
- D Candida glabrata; FKS1 mutations causing echinocandin resistance
Explanation
Invasive pulmonary aspergillosis (IPA) in neutropaenic hosts classically shows CT halo sign (haemorrhagic infarction around the fungal lesion) progressing to air-crescent sign as neutrophils recover. BAL galactomannan is a sensitive marker for IPA. Aspergillus fumigatus hyphae are septate with acute-angle (45°) branching. Voriconazole resistance in A. fumigatus is primarily mediated by point mutations in cyp51A encoding lanosterol 14α-demethylase (the azole target), particularly TR34/L98H and G54, M220 mutations. In voriconazole-refractory IPA, isavuconazole or liposomal amphotericin B are alternatives. Mucor hyphae are non-septate (pauciseptate) with right-angle branching, are intrinsically voriconazole-resistant but not as described here.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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