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      Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium

      research-article
      1 , 2 , 3 , 4 , 5 ,   6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 62 , 20 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 14 , 48 , 49 , 50 , 51 , 40 , 52 , 53 , 64 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 5
      Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
      Oxford University Press
      consensus, definitions, invasive fungal diseases, diagnosis, research

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          Abstract

          Background

          Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential.

          Methods

          To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups’ findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved.

          Results

          There is no change in the classifications of “proven,” “probable,” and “possible” IFD, although the definition of “probable” has been expanded and the scope of the category “possible” has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses.

          Conclusions

          These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

          Abstract

          European Organization for Research and Treatment of Cancer and the Mycoses Study Group definitions for probable invasive fungal disease now include solid organ transplant, hematologic malignancy, graft-versus-host disease, the reverse halo sign, revised thresholds for galactomannan, Aspergillus polymerase chain reaction, and definitions for candidiasis, cryptococcosis, non-human immunodeficiency viirus–associated pneumocystosis, and endemic mycoses.

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          Most cited references83

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          Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.

          Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
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            Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET).

            Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking. The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.
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              Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial.

              Isavuconazole is a novel triazole with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of isavuconazole versus voriconazole in patients with invasive mould disease.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press (US )
                1058-4838
                1537-6591
                15 September 2020
                05 December 2019
                05 December 2019
                : 71
                : 6
                : 1367-1376
                Affiliations
                [1 ] Department of Hematology , Radboudumc, Nijmegen, The Netherlands
                [2 ] Centre for Infectious Diseases and Microbiology, Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, University of Sydney , Sydney, Australia
                [3 ] Division of Infectious Diseases, University of Michigan, VA Ann Arbor Healthcare System , Ann Arbor, Michigan, USA
                [4 ] Department of Pediatrics, Duke University Medical Center , Durham, North Carolina, USA
                [5 ] Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham , Birmingham, Alabama, USA
                [6 ] Center of Expertise in Mycology Radboudumc/CWZ , Nijmegen, The Netherlands
                [7 ] University of Pittsburgh , Pittsburg, Pennsylvania, USA
                [8 ] Department of Medicine, University of Florida College of Medicine , Gainesville, Florida, USA
                [9 ] Mycotic Diseases Branch, Centers for Disease Control and Prevention , Atlanta, Georgia, USA
                [10 ] Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology and Oncology University Children’s Hospital , Münster, Germany
                [11 ] University of Sydney, Marie Bashir Institute for Infectious Diseases & Biosecurity, University of Sydney School of Medicine Faculty of Medicine and Health, Westmead Institute for Centre for Infectious Diseases and Microbiology, Western Sydney Local Health District , Sydney, Australia
                [12 ] Infectious Disease Clinic, Department of Medicine University of Udine and Department of Health Sciences, DISSAL, University of Genoa , Genoa, Italy
                [13 ] Ankara University, Faculty of Medicine, Cebeci Campus, Hematology Clinical Research Unit , Ankara, Turkey
                [14 ] Department of Medicine and Division of Infectious Diseases, Duke University Medical Center , Durham, North Carolina, USA
                [15 ] Division of Infectious Diseases, Departments of Medicine, Microbiology and Immunology School of Medicine and Public Health and School of Pharmacy, University of Wisconsin , Madison, Wisconsin, USA
                [16 ] Médicine Intensive et Réanimation Hôpital Saint-Louis, APHP, Université Paris Diderot , Paris, France
                [17 ] Molecular Diagnostics of Infectious Diseases, Microbiology, LADR Zentrallabor Dr. Kramer & Kollegen , Geesthacht, Germany
                [18 ] Division of Infectious Diseases, University of Arkansas for Medical Sciences , Little Rock, Arkansas, USA
                [19 ] Institut Pasteur, Molecular Mycology Unit, CNRS UMR2000, Mycology Laboratory, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris , Paris, France
                [20 ] Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne , Lausanne, Switzerland
                [21 ] Department of Medicine, Alpert Warren Medical School of Brown University , Providence, Rhode Island, USA
                [22 ] Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini , Genova, Italy
                [23 ] Infectious Diseases Unit, G. Fracastoro Hospital, San Bonifacio , Verona, Italy
                [24 ] Spanish National Centre for Microbiology, Instituto de Salud Carlos III , Madrid, Spain
                [25 ] Infectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland, USA
                [26 ] National Heart & Lung Institute, Imperial College London, the Royal Brompton & Harefield NHS Foundation Trust , London, UK
                [27 ] Pediatric Infectious Diseases Division at the Children’s Hospital of Philadelphia , Philadelphia, Pennsylvania, USA
                [28 ] Centre for Global Health, Institute for Infection and Immunity, St Georges University of London , London, UK
                [29 ] Diagnostic and Interventional Radiology, University Hospital Heidelberg, Translational Lung Research Center and Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik Heidelberg , Heidelberg, Germany
                [30 ] Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark
                [31 ] Centre for Medical Microbiology, University College London , London, UK
                [32 ] UT MD Anderson Cancer Center , Houston, Texas, USA
                [33 ] Radboud Center for Infectious Diseases and Department of Medicine , Radboudumc, Nijmegen, The Netherlands
                [34 ] Department of Microbiology, Immunology and Transplantation and Department of Laboratory Medicine and National Reference Centre for Mycosis, University Hospitals Leuven , Leuven, Belgium
                [35 ] Infectious Diseases Service, Department of Medicine and Institute of Microbiology, Lausanne University Hospital and University of Lausanne , Lausanne, Switzerland
                [36 ] Pediatric Hematology and Oncology, Hospital for Children and Adolescents, University of Frankfurt , Frankfurt, Germany
                [37 ] Molecular Biology and Infection, Medical Hospital II, WÜ4i, University Hospital Würzburg , Würzburg, Germany
                [38 ] Paris University, Necker Pasteur Center for Infectious Diseases and Tropical Medicine, IHU Imagine & Institut Pasteur, Molecular Mycology Unit , CNRS UMR 2000, Paris, France
                [39 ] Department of Hematology, University Hospitals Leuven , Leuven, Belgium
                [62 ] Department of Microbiology, Immunology and Transplantation , K.U. Leuven, Leuven, Belgium
                [40 ] Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School
                [41 ] Critical Care Medicine Department NIH-Clinical Center , Bethesda, Maryland, USA
                [42 ] Department of Medical Microbiology and Infectious Diseases and Centre of Expertise in Mycology Radboudumc/Canisius Wilhelmina Hospital , Nijmegen, The Netherlands
                [43 ] Alfred Health and Monash University , Melbourne, Australia
                [44 ] Department of Internal Medicine, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil
                [45 ] Division of Infectious Diseases, McGovern Medical School , Houston, Texas, USA
                [46 ] Istituto di Ematologia, Università Cattolica S. Cuore , Rome, Italy
                [47 ] UT Health San Antonio and South Texas Veterans Health Care System , San Antonio, Texas, USA
                [48 ] Department of Internal Medicine–Hematology and Oncology, Masaryk University and University Hospital Brno , Brno, Czech Republic
                [49 ] Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Hippokration General Hospital , Thessaloniki, Greece
                [50 ] Department of Hematology & Oncology, Lukas Hospital , Buende, Germany
                [51 ] Meander Medical Center Amersfoort and Radiology, Radboud University Medical Center , Nijmegen, The Netherlands
                [52 ] Department of Infectious Diseases, Peter MacCallum Cancer Center and the National Centre for Infections in Cancer, The University of Melbourne , Melbourne, Victoria, Australia
                [53 ] Division of Infectious Diseases and Geographic Medicine, Stanford University Medical School , Stanford, California
                [64 ] California Institute for Medical Research , San Jose, California, USA
                [54 ] Department of Internal Medicine, Division of Infectious Diseases, University of California Davis Medical Center , Sacramento, California, USA
                [55 ] Division of Infectious Diseases, Medical College of Georgia/Augusta University , Augusta, Georgia, USA
                [56 ] Division of Infectious Disease, University of Genova and San Martino University Hospital , Genova, Italy
                [57 ] Weill Cornell Medicine of Cornell University, Departments of Medicine, Pediatrics, Microbiology & Immunology , New York, New York, USA
                [58 ] MRC Centre for Medical Mycology at the University of Aberdeen , Aberdeen, UK
                [59 ] MiraVista Diagnostics , Indianapolis, Indiana, USA
                [60 ] Public Health Wales Mycology Reference Laboratory, University Hospital of Wales , Heath Park, Cardiff, UK
                [61 ] Perelman School of Medicine at the University of Pennsylvania, Children’s Hospital of Philadelphia and Roberts Center for Pediatric Research , Philadelphia, Pennsylvania, USA
                Author notes
                Correspondence: J. P. Donnelly, De Hoefkamp 1096, 6545 MD Nijmegen, The Netherlands ( p.donnelly@ 123456usa.net ).
                Article
                ciz1008
                10.1093/cid/ciz1008
                7486838
                31802125
                cdbcaebc-7022-468a-918a-95212d5d90de
                © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 May 2019
                : 08 October 2019
                : 05 December 2019
                Page count
                Pages: 10
                Categories
                Articles and Commentaries
                AcademicSubjects/MED00290

                Infectious disease & Microbiology
                consensus,definitions,invasive fungal diseases,diagnosis,research

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