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Breakthrough IFD on Azole Prophylaxis — SCE Infectious Diseases MCQ

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ModerateFungal InfectionsBreakthrough IFD on Azole ProphylaxisSCE Infectious Diseases

A 55-year-old man develops febrile neutropenia (neutrophils 0.2 × 10⁹/L) after chemotherapy for AML. He is started on Piperacillin/Tazobactam. At 96 hours he remains febrile. CT chest shows a new wedge-shaped peripheral consolidation. The microbiology registrar suggests starting empirical antifungals. He is already on Posaconazole prophylaxis. What is the most appropriate empirical antifungal choice?

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Correct answer: D — Liposomal Amphotericin B (or Caspofungin) — breakthrough IFD on azole prophylaxis requires a different antifungal class

Breakthrough fungal infection on azole prophylaxis mandates switching to a different antifungal class. Liposomal Amphotericin B (broad-spectrum, fungicidal) or an Echinocandin (Caspofungin, Micafungin) are appropriate empirical choices. Increasing or switching within the azole class is inappropriate — the breakthrough implies either azole-resistant organisms (e.g. Mucorales, which are intrinsically azole-resistant except Isavuconazole) or inadequate azole levels. TDM of the prophylactic azole should also be performed to assess whether levels were subtherapeutic.

Reference: ECIL-6 2017 – Empirical antifungal therapy; BSAC 2024 – Antifungal guidelines