A 48-year-old post-renal transplant patient on tacrolimus + prednisolone develops fever and pulmonary infiltrates. Serum galactomannan (GM) ELISA index is 1.8 (cut-off >0.5). Beta-D-glucan is also elevated. CT thorax shows a halo sign. Which antifungal should be started, and what is the limitation of the galactomannan test?

• A Fluconazole IV; galactomannan is specific for Candida and confirms candidaemia
• B Caspofungin IV; beta-D-glucan is specific for Aspergillus; galactomannan does not have clinical utility in transplant patients
• C Voriconazole IV; galactomannan is a cell wall polysaccharide of Aspergillus species and is the preferred biomarker for invasive aspergillosis; false positives can occur with piperacillin-tazobactam, mould-active antifungal prophylaxis, and other moulds (Fusarium, Histoplasma) ✓
• D Amphotericin B deoxycholate; galactomannan is useful but must be confirmed by bronchoscopy before starting treatment

Explanation

Halo sign on CT (ground-glass opacity surrounding a nodule representing haemorrhagic infarction) combined with elevated serum galactomannan (GM) index >0.5 in a haematology/transplant patient strongly suggests invasive pulmonary aspergillosis (IPA). Voriconazole IV is the drug of choice for IPA (IDSA/ESCMID guidelines). Galactomannan is a polysaccharide released from Aspergillus cell walls during active growth. Key limitations: false positives with piperacillin-tazobactam (degradation products), prior antifungal prophylaxis (reduces sensitivity), dietary sources, and other moulds like Fusarium, Paecilomyces, Histoplasma. Sensitivity is lower in solid-organ transplants than in neutropenic haematology patients. Beta-D-glucan is pan-fungal (does not detect Mucorales or Cryptococcus specifically). Fluconazole lacks activity against Aspergillus.

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

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