Antifungal prophylaxis and pre-emptive therapy: When and how?

Abstract

The growing pool of critically ill or immunocompromised patients leads to a constant increase of life-threatening invasive infections by fungi such as Aspergillus spp., Candida spp. and Pneumocystis jirovecii. In response to this, prophylactic and pre-emptive antifungal treatment strategies have been developed and implemented for high-risk patient populations. The benefit by risk reduction needs to be carefully weighed against potential harm caused by prolonged exposure against antifungal agents. This includes adverse effects and development of resistance as well as costs for the healthcare system. In this review, we summarise evidence and discuss advantages and downsides of antifungal prophylaxis and pre-emptive treatment in the setting of malignancies such as acute leukaemia, haematopoietic stem cell transplantation, CAR-T cell therapy, and solid organ transplant. We also address preventive strategies in patients after abdominal surgery and with viral pneumonia as well as individuals with inherited immunodeficiencies. Notable progress has been made in haematology research, where strong recommendations regarding antifungal prophylaxis and pre-emptive treatment are backed by data from randomized controlled trials, whereas other critical areas still lack high-quality evidence. In these areas, paucity of definitive data translates into centre-specific strategies that are based on interpretation of available data, local expertise, and epidemiology. The development of novel immunomodulating anticancer drugs, high-end intensive care treatment and the development of new antifungals with new modes of action, adverse effects and routes of administration will have implications on future prophylactic and pre-emptive approaches.

Keywords: Empiric treatment; Immunosuppression; Infection in haematology; Invasive fungal infection; Mycoses.

Conflict of interest statement

Declaration of competing interest RS has received speaker honoraria by Pfizer. DN has received research support from MSD and Pfizer and consulting fees from MSD, Pfizer, Basilea, and Gilead. MO works as Scientific Support Representative for Taconic Biosciences GmbH. JP has received honoraria from Associates of Cape Cod, Gilead Sciences, Swedish Orphan Biovitrum, and Pfizer, research funding from Merck & Co., and Pfizer and is a stakeholder of AbbVie Inc., and Novo Nordisk. OAC reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Abbvie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pardes, Pfizer, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Abbvie, Al-Jazeera Pharmaceuticals, Astellas, Gilead, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Noscendo, Pfizer, Shionogi; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, PSI, Pulmocide, Shionogi, The Prime Meridian Group; A patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Stocks from CoRe Consulting, and EasyRadiology. JS has received research grants by the Ministry of Education and Research (BMBF) and Basilea Pharmaceuticals Inc.; has received speaker honoraria by Pfizer Inc., Gilead and AbbVie; has been a consultant to Gilead, Produkt&Markt GmbH, Alvea Vax. And Micron Research, and has received travel grants by German Society for Infectious Diseases (DGI e.V.) and Meta-Alexander Foundation. JAN and IR have nothing to declare.

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.