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. 2024 Apr;50(4):502-515.
doi: 10.1007/s00134-024-07341-7. Epub 2024 Mar 21.

Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM

Matteo Bassetti  1   2 , Daniele R Giacobbe  3   4 , Christina Agvald-Ohman  5 , Murat Akova  6 , Ana Alastruey-Izquierdo  7   8 , Sevtap Arikan-Akdagli  9 , Elie Azoulay  10   11 , Stijn Blot  12   13 , Oliver A Cornely  14   15   16   17 , Manuel Cuenca-Estrella  7 , Dylan W de Lange  18 , Francesco G De Rosa  19 , Jan J De Waele  20 , George Dimopoulos  21 , Jose Garnacho-Montero  22 , Martin Hoenigl  23   24   25 , Souha S Kanj  26 , Philipp Koehler  14   27 , Bart J Kullberg  28 , Frédéric Lamoth  29   30   31 , Cornelia Lass-Flörl  32 , Johan Maertens  33 , Ignacio Martin-Loeches  34 , Patricia Muñoz  35   36   37   38 , Garyphallia Poulakou  39 , Jordi Rello  40   41   42   43 , Maurizio Sanguinetti  44   45 , Fabio S Taccone  46 , Jean-François Timsit  47   48 , Antoni Torres  49   50   51   52 , Jose A Vazquez  53 , Joost Wauters  54 , Erika Asperges  55 , Andrea Cortegiani  56   57 , Cecilia Grecchi  58 , Ilias Karaiskos  59 , Clément Le Bihan  60 , Toine Mercier  61   62 , Klaus L Mortensen  63 , Maddalena Peghin  64 , Chiara Rebuffi  65 , Sofia Tejada  40   43 , Antonio Vena  3   4 , Valentina Zuccaro  55 , Luigia Scudeller  66 , Thierry Calandra  30   31 ; Study Group for Infections in Critically Ill Patients of the European Society of Clinical Microbiology and Infectious Diseases (ESGCIP), the Fungal Infection Study Group of the European Society of Clinical Microbiology and Infectious Diseases (EFISG), the European Society of Intensive Care Medicine (ESICM), the European Confederation of Medical Mycology (ECMM), the Mycoses Study Group Education and Research Consortium (MSGERC), the International Society of Antimicrobial Chemotherapy (ISAC), the International Society for Human and Animal Mycology (ISHAM), the Austrian Society for Medical Mycology (ÖGMM), the Italian Society of Anesthesia, Analgesia, Reanimation, and Intensive Care (SIAARTI), the Italian Society of Anti-Infective Therapy (SITA), and the FUNDICU Collaborators
Collaborators, Affiliations

Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM

Matteo Bassetti et al. Intensive Care Med. 2024 Apr.

Abstract

Purpose: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs).

Methods: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method.

Results: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.

Keywords: Aspergillus; Candida; Consensus; Definitions; Diagnosis; Intensive care unit; Invasive fungal diseases; Research.

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Conflict of interest statement

Outside the submitted work, MB reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from BioMérieux, Cidara, Gilead, Menarini, MSD, Pfizer, and Shionogi. Outside the submitted work, DRG reports investigator-initiated grants from Pfizer Inc, Shionogi, BioMérieux, and Gilead Italia, and personal fees for advisor/speaker from Pfizer Inc., Menarini, and Tillotts Pharma. Outside the submitted work, AAI reports fees for educational lectures from Gilead, Pfizer, and MSD; grants from Instituto de Salud Carlos III and ESCMID; advisor for the Joint Program Initiative on Antimicrobial Resistance and the WHO Technical Expert Group for the Development of the Fungal Priority Pathogens List; travel support from Gilead. Outside the submitted work, EA reports grants from Pfizer and MSD, and honoraria for lectures or presentations from Gilead, Pfizer, Alexion, Mindray, and Sanofi. OAC reports grants or contracts from BMBF, Cidara, EU-DG RTD (101037867), F2G, Gilead, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Abbvie, AiCuris, Biocon, Cidara, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Moderna, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pfizer, PSI, Scynexis, Seres; honoraria for lectures from Abbot, Abbvie, Al-Jazeera Pharmaceuticals/Hikma Gilead, Grupo Biotascana/United Medical/Knight ISHAM Working group, MedScape, MedUpdate, Merck/MSD, Noscendo, Pfizer,Shionogi, StreamedUp; payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Boston Strategic Partners, Cidara, IQVIA, Janssen, MedPace, Pulmocide, Shionogi, PSI, The Prime Meridian Group; a pending patent currently reviewed at the German Patent and Trade Mark Office; stoke or stoke options from CoRe Consulting and EasyRadiology; other interests from Wiley, outside the submitted work. Outside the submitted work, FGDR reports consulting fess/honoraria for lectures from MSD, Pfizer, and Gilead Sciences, and travel fees from Pfizer and MSD. JDW reports grants for advisor/consultant or speaker/chairman from for MSD, Pfizer, and ThermoFisher (fees and honoraria paid to institution). GD reports honoraria for lectures/presentations from Gilead, Pfizer, and InfectoPharm. JGM reports personal fees for advisor/consultant and/or speaker/chairman from Gilead and Pfizer. MH received research funding from Gilead Sciences, Astellas, Mundipharma, Euroimmune, MSD, Pulmocide, IMMY, Scynexis, F2G and Pfizer, outside the submitted work. Outside the submitted work, SSK reports fees for lectures/advisory board from Basilea, MSD, Pfizer, and Hikma. PK reports grants or contracts from German Federal Ministry of Research and Education (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine (NUM) and the State of North Rhine-Westphalia; consulting fees Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited, Noxxon N.V. and Pfizer Pharma; honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., Datamed GmbH, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, HELIOS Kliniken GmbH, Lahn-Dill-Kliniken GmbH, medupdate GmbH, MedMedia GmbH, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC and University Hospital and LMU Munich; participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited and Pfizer Pharma; a pending patent currently reviewed at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. Outside the submitted work, FL reports grants from Pfizer, Gilead, MSD, Novartis, Swiss National Science Foundation, Santos-Suarez Foundation; and honoraria for lectures/presentation from Gilead, Pfizer, MSD, Mundipharma. Outside the submitted work, CLF reports research grants and/or personal fees for advisor/consultant, travel and/or speaker/chairman from Gilead, MSD, Pfizer, BioMérieux, F2G, IMMY, Shionogi, Astellas Pharma. Outside the submitted work, JM reports research grants and/or personal fees for advisor/consultant, and/or speaker/chairman from Gilead Sciences, F2G, Shionogi, Mundipharma, Mundipharma, Takeda, and Basilea. Outside the submitted work, IML reports grants from Grifols; consulting fees from MSD, Gilead, Mundipharma, fees for lectures/advisory board from Gilead, MSD, and Mundipharma; travel support from the European Respiratory Society (Chair Critical Care Group). Outside the submitted work, PM reports fees for lectures/advisory board from Gilead, MSD, Mundipharma, Pfizer. Outside of the submitted work, GP reports fees for lectures/advisory board from AstraZeneca, Gilead, Glaxo, Menarini, MSD, Pfizer and SOBI; grants from Adagio Therapeutics, AstraZeneca, Bausch, Fabentech, Pfizer, PharmaMar, Roche, Xenothera. Outside the submitted work, JR reports consulting fees from Pfizer; honoraria for lectures/presentations from Pfizer, MSD, and Roche; travel support from Roche. Outside the submitted work, J-FT reports grants from Pfizer and MSD; consulting fees from Gilead; honoraria for lectures/presentations from Mundipharma, Gilead, and Pfizer; Advisor fees from MSD, Pfizer, BD, Aspen, Roche diagnostic, and BioMérieux. Outside the submitted work, AT reports consultant/speaker fees from Pfizer, Poliphor, MSD, Jansen, and OM Pharma. Outside the submitted work, JAV reports consulting fees from F2G and Cidara; honoraria for lectures/presentations from Melinta. Outside the submitted work, JW reports investigator-initiated research grants, speaker honoraria and travel grants from Pfizer and Gilead. Outside the submitted work, AC reports fees for lectures/advisory board from Gilead, MSD, Mundipharma, Pfizer. Outside the submitted work, IK reports grants and honoraria for lectures/presentations from Pfizer and BioMérieux. Outside the submitted work, TM reports consultancy fees from Gilead Sciences, Pfizer and AstraZeneca, unrestricted research grants from Gilead Sciences, and travel support from AstraZeneca. Outside the submitted work, KM reports travel support from Gilead. Outside the submitted work, MP reports honoraria for lectures/presentations from Dia Sorin, MDS, Menarini, Pfizer, and ThermoFisher. Outside the submitted work, LS reports travel support from ESCMID. TC has participated in advisory/safety monitoring boards or consulted for Cidara, Novartis, MSD Merck Sharp & Dohme AG, Shionogi and Gilead and received grant from European Community (Horizon 2020, HDM-FUN Grant; host-directed medicine in invasive fungal infections, co-applicant) for projects unrelated to the submitted work; all contracts were made with and fees paid to his institution (CHUV).

Figures

Fig. 1
Fig. 1
Flowchart for probable deep-seated candidiasis research definition in non-neutropenic, adult patients in ICU. The definitions of probable IC provided in the present document do not apply to those ICU patients fulfilling host factors as defined in the European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group Education and Research Consortium (MSGERC) consensus: (i) hematology and solid organ transplantation patients; (ii) prolonged use of corticosteroids; (iii) treatment with other recognized T-cell immunosuppressants; (iv) treatment with recognized B-cell immunosuppressants; (v) inherited severe immunodeficiency; (vi) acute graft-versus-host disease grade III or IV involving the gut, lungs, or liver that is refractory to first-line treatment with steroids. In these patients, the EORTC/MSGERC definitions should be used for defining IC in research studies (for more details, see the EORTC/MSGERC consensus document [20]). aSuch abnormalities should be evident in deep sites where invasive candidiasis may develop either because of direct inoculation or because of previous, undetected hematogenous spread (e.g., IAC, endocarditis, osteomyelitis, arthritis, mediastinitis, meningitis; with the exclusion of the lung, for which only a proven diagnosis through histology would be considered as invasive candidiasis). The investigations carried out for excluding alternative diagnoses should be reported in detail. b Specimens should be obtained during surgery, puncture, or obtained from a newly inserted drain as soon as possible (no later than 24 h after placement). This mycological criterion does not apply to the isolation of Candida spp. from peritoneal fluid after gastrointestinal/urogenital perforation if complete source control is rapidly obtained (within 24 h from perforation and after peritoneal fluid collection). This may reflect contamination before development of invasive disease and does not define a mycological criterion for probable deep-seated candidiasis. In case of source control performed > 24 h after perforation or in case of recurrent peritonitis (e.g., anastomosis leakage), isolation of Candida spp. from the peritoneum (from an intra-abdominal specimen during surgery or obtained from an external drainage inserted from < 24 h) does define a mycological criterion for probable deep-seated candidiasis. The same concepts apply to Candida mediastinitis and pleuritis/pleural empyema after esophageal perforation. c The presence of concomitant proven candidemia can be considered as a mycological criterion for probable deep-seated candidiasis. In this case, the disease should be classified as proven IC in research studies (proven candidemia plus probable deep-seated candidiasis). IC invasive candidiasis, ICU intensive care unit
Fig. 2
Fig. 2
Flowchart for probable IPA and probable TBA research definitions in non-neutropenic, adult patients in ICU*. BALF bronchoalveolar lavage fluid, COPD chronic obstructive pulmonary disease, COVID-19 coronavirus disease 2019, CT computerized tomography, GM galactomannan, HIV human immunodeficiency virus, ICU intensive care unit, IPA invasive pulmonary aspergillosis, ODI optical density index, TBA tracheobronchial aspergillosis. *The definitions of probable IPA/TBA for research studies provided in the present document do not apply to those ICU patients fulfilling host factors as defined in the EORTC/MSGERC consensus: (i) hematology and solid organ transplant patients; (ii) prolonged use of corticosteroids; (iii) treatment with other recognized T-cell immunosuppressants; (iv) treatment with recognized B-cell immunosuppressants; (v) inherited severe immunodeficiency; (vi) acute graft-versus-host disease grade III or IV involving the gut, lungs, or liver that is refractory to first-line treatment with steroids. In these patients, the EORTC/MSGERC definitions should be used for defining IPA/TBA in research studies (for more details, see the EORTC/MSGERC consensus document [20]). aPlatelia Aspergillus Ag Kit. bWhen the Platelia test is unavailable, another GM test can be used when this test was compared with the Platelia test in a well-designed study and shown to have comparable specificity to the 1.0 Platelia cut-off. cCompatible with the site/progression of IPA or TBA. dNot applicable for patients ventilated patients from more than 48 h at the time of assessment for probable IPA/TBA. TBA; applicable in the first 48 h if dyspneic at the time of initiation of ventilation
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