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. 2025 Oct;68(10):e70123.
doi: 10.1111/myc.70123.

Breakthrough Invasive Mould Infections Under Posaconazole Prophylaxis in Patients With Haematologic Malignancies: A Case-Control Study

Camille Marchetti  1 , Emmanouil Glampedakis  1 , Jannik Stemler  2   3   4 , Luise Hänsel  2   3   4 , Sabine Kuster  5 , Ilona Kronig  6 , Katia Boggian  7 , Nina Khanna  5 , Dionysios Neofytos  6 , Oliver A Cornely  2   3   4 , Frederic Lamoth  1   8 ; Fungal Infection Network of Switzerland (FUNGINOS)
Collaborators, Affiliations

Breakthrough Invasive Mould Infections Under Posaconazole Prophylaxis in Patients With Haematologic Malignancies: A Case-Control Study

Camille Marchetti et al. Mycoses. 2025 Oct.

Abstract

Background: Posaconazole (POS) prophylaxis is recommended for the prevention of invasive mould infections among patients with haematologic cancer and prolonged neutropenia or following allogeneic haematopoietic cell transplantation. Albeit rare, breakthrough invasive mould infections (bIMI) are associated with high mortality rates.

Objectives: To assess the epidemiology, causes and outcomes of bIMI under POS prophylaxis.

Patients/methods: Haematologic cancer patients with a diagnosis of proven/probable bIMI while receiving POS prophylaxis for ≥ 7 days were retrospectively included in five hospitals (Switzerland and Germany). For each bIMI case, one to two non-bIMI controls receiving POS prophylaxis for the same haematologic condition were included.

Results: A total of 29 bIMI episodes and 46 controls were included. Baseline characteristics and median POS trough concentrations did not significantly differ between the two groups. Invasive aspergillosis was the most frequent bIMI (52%), followed by invasive mucormycosis (31%). POS non-susceptible pathogens were the causes of bIMI in 14% of cases. While insufficient POS exposure was observed in 39% of bIMI cases, this proportion was similar in the control group. Most bIMI were treated with liposomal amphotericin B first-line therapy and received multiple antifungal therapies. Overall mortality was significantly higher among bIMI compared to controls (52% vs. 20%, p = 0.005). Surgery was the only parameter significantly associated with survival.

Conclusions: This case-control study shows that bIMI is associated with a significant impact on mortality. Most bIMI were attributed to presumably POS-susceptible pathogens without a clear association with POS underexposure. The causes of bIMI remain unclear and may be the conjunction of multiple parameters.

Keywords: amphotericin B; antifungal prophylaxis; invasive fungal diseases; leukaemia; triazoles.

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Conflict of interest statement

Nina Khanna reports honoraria for conferences, data safety monitoring boards or advisory boards from Gilead, MSD, Pfizer, Idorsia, Takeda and Pulmocide, outside of the present work. Oliver A. Cornely reports grants or contracts from iMi, iHi, DFG, BMBF, Cidara, DZIF, EU‐DG RTD, F2G, Gilead, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; consulting fees from Abbvie, AiCuris, Basilea, Biocon, Boston Strategic Partners, Cidara, Elion Therapeutics, Gilead, GSK, IQVIA, Janssen, Matinas, MedPace, Menarini, Melinta, Molecular Partners, MSG‐ERC, Mundipharma, Noxxon, Octapharma, Pardes, Pfizer, PSI, Scynexis, Seres, Seqirus, Shionogi, The Prime Meridian Group; speaker and lecture honoraria from Abbott, Abbvie, Akademie für Infektionsmedizin, Al‐Jazeera Pharmaceuticals/Hikma, amedes, AstraZeneca, Deutscher Ärzteverlag, Gilead, GSK, Grupo Biotoscana/United Medical/Knight, InfectoPharm, Ipsen Pharma, Medscape/WebMD, MedUpdate, MSD, Moderna, Mundipharma, Noscendo, Paul‐Martini‐Stiftung, Pfizer, Sandoz, Seqirus, Shionogi, streamedup!, Touch Independent, Vitis; payment for expert testimony Cidara; participation on a DRC, DSMB, DMC, Advisory Board for AstraZeneca, Cidara, IQVIA, Janssen, MedPace, Melinta, PSI, Pulmocide, Vedanta Biosciences. Frederic Lamoth reports research funding from Pfizer and Novartis, and honoraria for conferences or advisory boards from Gilead, MSD, Pfizer, Mundipharma and Becton‐Dickinson, outside of the present work. All contracts were made with and fees paid to his institution (CHUV).

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