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Breakthrough Invasive Mould Infections Under Posaconazole Prophylaxis in Patients With Haematologic Malignancies: A

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Breakthrough invasive mould infections (bIMI) in patients on posaconazole (POS) prophylaxis significantly increase mortality. Causes remain unclear, often involving POS-susceptible pathogens without clear POS underexposure.

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Area of Science:

  • Mycology
  • Hematology
  • Infectious Diseases

Background:

  • Posaconazole (POS) prophylaxis is standard for preventing invasive mould infections (IMIs) in high-risk hematologic cancer patients.
  • Breakthrough IMIs (bIMI) under POS prophylaxis, though rare, carry high mortality rates.

Purpose of the Study:

  • To investigate the epidemiology, causative agents, and outcomes of bIMI in patients receiving POS prophylaxis.
  • To compare characteristics and outcomes of bIMI cases with non-bIMI control patients on POS prophylaxis.

Main Methods:

  • Retrospective case-control study including 29 bIMI episodes and 46 controls across five hospitals in Switzerland and Germany.
  • Patients had proven/probable bIMI while on POS prophylaxis for at least 7 days; controls received POS for similar hematologic conditions.

Main Results:

  • Invasive aspergillosis (52%) and mucormycosis (31%) were the most common bIMI.
  • 14% of bIMI were caused by POS non-susceptible pathogens; insufficient POS exposure was noted in 39% of cases, similar to controls.
  • bIMI patients had significantly higher overall mortality (52% vs. 20%) compared to controls; surgery was linked to survival.

Conclusions:

  • bIMI significantly increases mortality in hematologic cancer patients on POS prophylaxis.
  • The exact causes of bIMI are multifactorial and not clearly linked to POS underexposure, even with presumably susceptible pathogens.