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Publications

Journal Article Review Ppublish 35 citations

PubMed: 38602408 DOI: 10.1128/cmr.00074-23

Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease.

Clin Microbiol Rev 37(2):e0007423

Authors: Martin Hoenigl, Amir Arastehfar, Maiken Cavling Arendrup, Roger Brüggemann, Agostinho Carvalho, Tom Chiller, Sharon Chen, Matthias Egger, Simon Feys, Jean-Pierre Gangneux, Jeremy A W Gold, Andreas H Groll, Jannes Heylen, Jeffrey D Jenks, Robert Krause, Katrien Lagrou, Frédéric Lamoth, Juergen Prattes, Sarah Sedik, Joost Wauters, Nathan P Wiederhold, George R Thompson

Affiliations

  • Department of Internal Medicine, Division of Infectious Diseases, ECMM Excellence Center for Medical Mycology, Medical University of Graz, Graz, Austria.
  • BiotechMed-Graz, Graz, Austria.
  • Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
  • Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark.
  • Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
  • Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Department of Pharmacy and Radboudumc Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Radboudumc-CWZ Center of Expertise in Mycology, Nijmegen, The Netherlands.
  • Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
  • ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
  • Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  • Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW South Wales Health Pathology, Westmead Hospital, Westmead, Australia.
  • The University of Sydney, Sydney, Australia.
  • Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium.
  • Centre National de Référence des Mycoses et Antifongiques LA-AspC Aspergilloses chroniques, European Excellence Center for Medical Mycology (ECMM EC), Centre hospitalier Universitaire de Rennes, Rennes, France.
  • Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) UMR_S 1085, Rennes, France.
  • Department of Pediatric Hematology/Oncology and Infectious Disease Research Program, Center for Bone Marrow Transplantation, University Children's Hospital, Muenster, Germany.
  • Department of Public Health, Durham County, Durham, North Carolina, USA.
  • Department of Medicine, Division of Infectious Diseases, Duke University, Durham, North Carolina, USA.
  • Department of Laboratory Medicine and National Reference Center for Mycosis, University Hospitals Leuven, Leuven, Belgium.
  • Department of Laboratory Medicine and Pathology, Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Department of Medicine, Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
  • Department of Internal Medicine, Division of Infectious Diseases University of California-Davis Medical Center, Sacramento, California, USA.
  • Department of Medical Microbiology and Immunology, University of California-Davis, Davis, California, USA.

Abstract

SUMMARYFungal infections are on the rise, driven by a growing population at risk and climate change. Currently available antifungals include only five classes, and their utility and efficacy in antifungal treatment are limited by one or more of innate or acquired resistance in some fungi, poor penetration into "sequestered" sites, and agent-specific side effect which require frequent patient reassessment and monitoring. Agents with novel mechanisms, favorable pharmacokinetic (PK) profiles including good oral bioavailability, and fungicidal mechanism(s) are urgently needed. Here, we provide a comprehensive review of novel antifungal agents, with both improved known mechanisms of actions and new antifungal classes, currently in clinical development for treating invasive yeast, mold (filamentous fungi), infections, and dimorphic fungi (endemic mycoses). We further focus on inhaled antifungals and the role of immunotherapy in tackling fungal infections, and the specific PK/pharmacodynamic profiles, tissue distributions as well as drug-drug interactions of novel antifungals. Finally, we review antifungal resistance mechanisms, the role of use of antifungal pesticides in agriculture as drivers of drug resistance, and detail detection methods for antifungal resistance.

MeSH

Pharmaceutical Preparations, Microbiology, Mycoses, Fungi, Therapeutics, Infections

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