Diagnosis of Breakthrough Fungal Infections in the Clinical Mycology Laboratory: An ECMM Consensus Statement
Jeffrey D. Jenks,Jean-Pierre Gangneux,Ilan S. Schwartz,Ana Alastruey-Izquierdo,Katrien Lagrou,George Richard Thompson,Cornelia Lass-Flörl,Martin Hoenigl,Martin Hoenigl +8 more
TLDR
A need exists for diagnostic tests that are effective, simple, cheap, and rapid to enable the diagnosis of bIFI in patients taking antifungals and support the design of future clinical trials in the field of clinical mycology.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.read more
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The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.
Martin Hoenigl,Martin Hoenigl,Rosanne Sprute,Matthias Egger,Amir Arastehfar,Oliver A. Cornely,Robert Krause,Cornelia Lass-Flörl,Juergen Prattes,Andrej Spec,George Richard Thompson,Nathan P. Wiederhold,Jeffrey D. Jenks +12 more
TL;DR: In this article, the authors describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a dihyroorotate dehydrogenase enzyme inhibitor) and opelconazole (a triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly).
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Aspergillosis: Epidemiology, Diagnosis, and Treatment.
TL;DR: The spectrum of disease produced by Aspergillus species ranges from allergic syndromes to chronic pulmonary conditions and invasive infections as mentioned in this paper, which is a major cause of morbidity and mortality in immunocompromised patients.
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Serology anno 2021-fungal infections: from invasive to chronic.
TL;DR: In this article, the authors provided an updated inventory of fungal antigen and serology tests for diagnosing invasive and chronic fungal infections, the key focus was set on Aspergillus, Candida and Cryptococcus species.
Journal ArticleDOI
Invasive aspergillosis in critically ill patients: Review of definitions and diagnostic approaches.
TL;DR: Invasive aspergillosis (IA) is an increasingly recognised phenomenon in critically ill patients in the intensive care unit, including in patients with severe influenza and severe coronavirus disease 2019 (COVID-19) infection as mentioned in this paper.
Journal ArticleDOI
Specificity Influences in (1→3)-β-d-Glucan-Supported Diagnosis of Invasive Fungal Disease
TL;DR: In this article, a review of the non-IFD related causes of elevated circulating β-glucan (BDG) is presented, including iatrogenic patient contamination through the use of BDG-containing medical devices and parenterally delivered materials as well as translocation of intestinal luminal BDG due to mucosal barrier injury.
References
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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
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TL;DR: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.
Journal ArticleDOI
Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline
Andrew J. Ullmann,José María Aguado,S. Arikan-Akdagli,David W. Denning,Andreas H. Groll,Katrien Lagrou,Cornelia Lass-Flörl,Russell E. Lewis,Patricia Muñoz,Paul E. Verweij,Adilia Warris,Florence Ader,Florence Ader,Murat Akova,Maiken Cavling Arendrup,Rosemary Ann Barnes,Catherine Beigelman-Aubry,Catherine Beigelman-Aubry,Stijn Blot,Stijn Blot,Stijn Blot,Emilio Bouza,Roger J. M. Brüggemann,Dieter Buchheidt,Jacques Cadranel,Jacques Cadranel,Elio Castagnola,Arunaloke Chakrabarti,Manuel Cuenca-Estrella,George Dimopoulos,George Dimopoulos,Jesús Fortún,Jean-Pierre Gangneux,Jorge Garbino,Werner J. Heinz,Raoul Herbrecht,Claus Peter Heussel,Christopher C. Kibbler,Nikolay Klimko,Bart Jan Kullberg,Christoph Lange,Thomas Lehrnbecher,Jürgen Löffler,Olivier Lortholary,J Maertens,O. Marchetti,Jacques F. Meis,Livio Pagano,Patricia Ribaud,Malcolm Richardson,Emmanuel Roilides,Markus Ruhnke,Maurizio Sanguinetti,Donald C. Sheppard,János Sinkó,Anna Skiada,Maria J G T Vehreschild,Claudio Viscoli,Oliver A. Cornely +58 more
TL;DR: Treatment duration for aspergillosis is strongly recommended based on clinical improvement, degree of immunosuppression and response on imaging, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended.
Journal ArticleDOI
Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium
Oliver A. Cornely,Ana Alastruey-Izquierdo,Dorothee Arenz,Sharon C.-A. Chen,Eric Dannaoui,Bruno Hochhegger,Bruno Hochhegger,Martin Hoenigl,Martin Hoenigl,Henrik Jeldtoft Jensen,Katrien Lagrou,Russell E. Lewis,Sibylle C. Mellinghoff,Mervyn Mer,Zoi D. Pana,Danila Seidel,Donald C. Sheppard,Roger Wahba,Murat Akova,Alexandre Alanio,Abdullah M. S. Al-Hatmi,Sevtap Arikan-Akdagli,Hamid Badali,Ronen Ben-Ami,Alexandro Bonifaz,Stéphane Bretagne,Elio Castagnola,Methee Chayakulkeeree,Arnaldo Lopes Colombo,Dora E. Corzo-Leon,Lubos Drgona,Andreas H. Groll,Jesús Guinea,Jesús Guinea,Claus Peter Heussel,Ashraf S. Ibrahim,Souha S. Kanj,Nikolay Klimko,Michaela Lackner,Frédéric Lamoth,Fanny Lanternier,Cornelia Lass-Floerl,Dong-Gun Lee,Thomas Lehrnbecher,Badre E. Lmimouni,Mihai Mares,Georg Maschmeyer,Jacques F. Meis,Joseph Meletiadis,Joseph Meletiadis,C. Orla Morrissey,Marcio Nucci,Rita O. Oladele,Livio Pagano,Alessandro C. Pasqualotto,Atul Patel,Zdenek Racil,Malcolm Richardson,Emmanuel Roilides,Markus Ruhnke,Seyedmojtaba Seyedmousavi,Seyedmojtaba Seyedmousavi,Neeraj Sidharthan,Nina Singh,Janos Sinko,Anna Skiada,Monica A. Slavin,Monica A. Slavin,Rajeev Soman,Brad Spellberg,William J. Steinbach,Ban Hock Tan,Andrew J. Ullmann,Joerg J. Vehreschild,Maria J G T Vehreschild,Thomas J. Walsh,P. Lewis White,Nathan P. Wiederhold,Theoklis E. Zaoutis,Arunaloke Chakrabarti +79 more
TL;DR: Management of mucormycosis depends on recognising disease patterns and on early diagnosis, and limited availability of contemporary treatments burdens patients in low and middle income settings.
Journal ArticleDOI
Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry.
Dionissios Neofytos,D. Horn,Elias Anaissie,William J. Steinbach,Ali J. Olyaei,Jay A. Fishman,M. A. Pfaller,C. Chang,K. Webster,Kieren A. Marr,Kieren A. Marr +10 more
TL;DR: IA remains the most commonly identified IFI among HSCT recipients, but rates of survival in persons with IA appear to have improved, compared with previously reported data.
Journal ArticleDOI
Multicenter Clinical Evaluation of the (1→3) β-D-Glucan Assay as an Aid to Diagnosis of Fungal Infections in Humans
Luis Ostrosky-Zeichner,Barbara D. Alexander,Daniel H. Kett,Jose A. Vazquez,Peter G. Pappas,Fumihiro Saeki,Paul A. Ketchum,John R. Wingard,Robert Schiff,Hiroshi Tamura,Malcolm A. Finkelman,John H. Rex,John H. Rex +12 more
TL;DR: In this paper, a single sample was obtained per patient and was evaluated using an assay to detect serum β-D-glucan derived from fungal cell walls (range, 0 to > 7000 pg/mL).
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