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. 2020 Oct 11;6(4):216.
doi: 10.3390/jof6040216.

Diagnosis of Breakthrough Fungal Infections in the Clinical Mycology Laboratory: An ECMM Consensus Statement

Jeffrey D Jenks  1   2   3 , Jean-Pierre Gangneux  4 , Ilan S Schwartz  5 , Ana Alastruey-Izquierdo  6 , Katrien Lagrou  7   8 , George R Thompson Iii  9 , Cornelia Lass-Flörl  10 , Martin Hoenigl  2   3   11 ; European Confederation of Medical Mycology (ECMM) Council Investigators
Collaborators, Affiliations

Diagnosis of Breakthrough Fungal Infections in the Clinical Mycology Laboratory: An ECMM Consensus Statement

Jeffrey D Jenks et al. J Fungi (Basel). .

Abstract

Breakthrough invasive fungal infections (bIFI) cause significant morbidity and mortality. Their diagnosis can be challenging due to reduced sensitivity to conventional culture techniques, serologic tests, and PCR-based assays in patients undergoing antifungal therapy, and their diagnosis can be delayed contributing to poor patient outcomes. In this review, we provide consensus recommendations on behalf of the European Confederation for Medical Mycology (ECMM) for the diagnosis of bIFI caused by invasive yeasts, molds, and endemic mycoses, to guide diagnostic efforts in patients receiving antifungals and support the design of future clinical trials in the field of clinical mycology. The cornerstone of lab-based diagnosis of breakthrough infections for yeast and endemic mycoses remain conventional culture, to accurately identify the causative pathogen and allow for antifungal susceptibility testing. The impact of non-culture-based methods are not well-studied for the definite diagnosis of breakthrough invasive yeast infections. Non-culture-based methods have an important role for the diagnosis of breakthrough invasive mold infections, in particular invasive aspergillosis, and a combination of testing involving conventional culture, antigen-based assays, and PCR-based assays should be considered. Multiple diagnostic modalities, including histopathology, culture, antibody, and/or antigen tests and occasionally PCR-based assays may be required to diagnose breakthrough endemic mycoses. A need exists for diagnostic tests that are effective, simple, cheap, and rapid to enable the diagnosis of bIFI in patients taking antifungals.

Keywords: breakthrough invasive fungal infections; diagnostics; endemic mycoses; invasive candidiasis; invasive mold infections.

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Conflict of interest statement

MH received grant funding from Gilead and Pfizer. JPG received grant funding from Pfizer. CLF received grants from Gilead, Pfizer, and Basilea, however, these funders have no influence on this manuscript. ISS has received an honorarium for serving on an advisory board from AVIR Inc. outside of the submitted work. GRT received consulting and research support from Amplyx, Astellas, Cidara, F2G, Mayne, Scynexis, and research support from Gilead, Merck, Regeneron, and Pfizer outside the submitted work. A.A.-I. has received research grants or honoraria as a speaker from Astellas, Gilead Sciences, MSD, Pfizer, F2G, Amplyx, and Scynexis outside the submitted work. KL received MSD, SMB Laboratoires Brussels, and Gilead; travel support from Pfizer and MSD; speaker fees from Gilead, FUJIFILM WAKO, and Pfizer; and a grant from Thermo Fisher Scientific, outside the submitted work. SAA reports speaker honoraria or travel grant from Astellas, Gilead, and Pfizer outside the submitted work. ER has received research grants from Astellas, Gilead, Merck, and Pfizer Inc.; he is a scientific advisor and member of speaker bureaus for Astellas, Gilead, Merck, and Pfizer Inc. OAC is supported by the German Federal Ministry of Research and Education, is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—CECAD, EXC 2030–390661388 and has received research grants from Actelion, Amplyx, Astellas, Basilea, Cidara, Da Volterra, F2G, Gilead, Janssen, Medicines Company, Melinta, Merck/MSD, Octapharma, Pfizer, Scynexis, is a consultant to Actelion, Allecra, Amplyx, Astellas, Basilea, Biosys, Cidara, Da Volterra, Entasis, F2G, Gilead, Matinas, MedPace, Menarini, Merck/MSD, Mylan, Nabriva, Noxxon, Octapharma, Paratek, Pfizer, PSI, Roche Diagnostics, Scynexis, and Shionogi, and received lecture honoraria from Al-Jazeera Pharmaceuticals, Astellas, Basilea, Gilead, Grupo Biotoscana, Merck/MSD, and Pfizer. ER has received research grants from Astellas, Gilead, Merck, and Pfizer Inc.; he is a scientific advisor and member of speaker bureaus for Astellas, Gilead, Merck, and Pfizer Inc. All other authors have no potential conflicts of interest to disclose. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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