New) Methods for Detection of Aspergillus fumigatus Resistance in Clinical Samples.
TLDR
New molecular-based approaches for detecting triazole resistance to Aspergillus, real-time polymerase chain reaction (PCR) to detect mutations to the Cyp51A protein, have been developed which are able to detect mostTriazole-resistant A. fumigatus strains in patients with invasive aspergillosis.Abstract:
The incidence of invasive aspergillosis has increased substantially over the past few decades, accompanied by a change in susceptibility patterns of Aspergillus fumigatus with increasing resistance observed against triazole antifungals, including voriconazole and isavuconazole, the most commonly used antifungal agents for the disease. Culture-based methods for determining triazole resistance are still the gold standard but are time consuming and lack sensitivity. We sought to provide an update on non-culture-based methods for detecting resistance patterns to Aspergillus. New molecular-based approaches for detecting triazole resistance to Aspergillus, real-time polymerase chain reaction (PCR) to detect mutations to the Cyp51A protein, have been developed which are able to detect most triazole-resistant A. fumigatus strains in patients with invasive aspergillosis. Over the last few years, a number of non-culture-based methods for molecular detection of Aspergillus triazole resistance have been developed that may overcome some of the limitations of culture. These molecular methods are therefore of high epidemiological and clinical relevance, mainly in immunocompromised patients with hematological malignancies, where culture has particularly limited sensitivity. These assays are now able to detect most triazole-resistant Aspergillus fumigatus strains. Given that resistance rates vary, clinical utility for these assays still depends on regional resistance patterns.read more
Citations
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Journal ArticleDOI
Aspergillus fumigatus and aspergillosis: From basics to clinics.
Amir Arastehfar,Agostinho Carvalho,Jos Houbraken,Lisa Lombardi,Rocio Garcia-Rubio,Jeffrey D. Jenks,Olga Rivero-Menendez,R. Aljohani,Ilse D. Jacobsen,J. Berman,N. Osherov,Mohammad Taghi Hedayati,Macit Ilkit,Darius Armstrong-James,Toni Gabaldón,J. Meletiadis,M. Kostrzewa,Weihua Pan,Cornelia Lass-Flörl,David S. Perlin,Martin Hoenigl,Martin Hoenigl +21 more
TL;DR: In this article, the authors comprehensively discuss the current clinical challenges caused by A. fumigatus and provide insights on how to address them and provide a continuous quest for novel antifungal drugs.
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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
Detecting Azole-Antifungal Resistance in Aspergillus fumigatus by Pyrosequencing.
TL;DR: Current diagnostic methods are reviewed and the potential of pyrosequencing to aid in a diagnosis complete with a resistance profile to improve clinical outcomes is highlighted.
Journal ArticleDOI
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
TL;DR: 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.
Journal ArticleDOI
Fungal Infections Diagnosis – Past, Present and Future
TL;DR: A review of the main steps of the diagnosis for systemic fungal infection, from diagnostic classifications, through methodologies considered as the gold standard, to the molecular methods currently used, and finally mentioning some of the more futuristic approaches is presented in this paper.
References
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Journal ArticleDOI
Azole fungicides - understanding resistance mechanisms in agricultural fungal pathogens.
TL;DR: An overview of the problem is given and the mechanisms that mediate azole resistance in agriculture are discussed (point mutations in the CYP51 amino acid sequence, overexpression of the CyP51 enzyme and overexpressing of genes encoding efflux pump proteins).
Journal ArticleDOI
Emergence of azole-resistant invasive aspergillosis in HSCT recipients in Germany
Joerg Steinmann,Axel Hamprecht,Maria J G T Vehreschild,Oliver A. Cornely,Dieter Buchheidt,Birgit Spiess,Michael Koldehoff,Jan Buer,Jacques F. Meis,Peter-Michael Rath +9 more
TL;DR: The emergence of azole-resistant IA with TR34/L98H and TR46/Y121F/T289A mutations in HSCT patients in Germany is highlighted and underscores the need for systematic antifungal susceptibility testing of A. fumigatus.
Journal ArticleDOI
MALDI‐TOF MS‐based drug susceptibility testing of pathogens: The example of Candida albicans and fluconazole
Carine Marinach,Alexandre Alanio,Alexandre Alanio,Martine Palous,Stéphanie Kwasek,Stéphanie Kwasek,Arnaud Fekkar,Arnaud Fekkar,Jean-Yves Brossas,Jean-Yves Brossas,Sophie Brun,Sophie Brun,Georges Snounou,Georges Snounou,Georges Snounou,Christophe Hennequin,Christophe Hennequin,Dominique Sanglard,Annick Datry,Jean-Louis Golmard,Dominique Mazier,Dominique Mazier +21 more
TL;DR: This work extendedMALDI‐TOF MS application to a novel assay of Candida albicans susceptibility to fluconazole, based on monitoring modifications of the proteome of yeast cells grown in the presence of varying drug concentrations, and showed full agreement with the Clinical Laboratory Standards Institute's reference method.
Journal ArticleDOI
Validation of a New Aspergillus Real-Time PCR Assay for Direct Detection of Aspergillus and Azole Resistance of Aspergillus fumigatus on Bronchoalveolar Lavage Fluid
G. M. Chong,Wendy W. J. van de Sande,Gijs Dingemans,Giel Gaajetaan,Alieke G. Vonk,Marie-Pierre Hayette,Dennis van Tegelen,Guus Simons,Bart J. A. Rijnders +8 more
TL;DR: The AsperGenius multiplex real-time PCR assay allows for sensitive and fast detection of Aspergillus species directly from BAL fluid samples and differentiates wild-type from resistant strains, even if BAL fluid cultures remain negative.
Journal ArticleDOI
Diagnosis of invasive aspergillosis by a commercial real-time PCR assay for Aspergillus DNA in bronchoalveolar lavage fluid samples from high-risk patients compared to a galactomannan enzyme immunoassay
Riccardo Torelli,Maurizio Sanguinetti,Adrian Moody,Livio Pagano,Morena Caira,Elena De Carolis,Leonello Fuso,Gennaro De Pascale,Giuseppe Bello,Massimo Antonelli,Giovanni Fadda,Brunella Posteraro +11 more
TL;DR: The MycAssay Aspergillus PCR appears to be a sensitive and specific molecular test for the diagnosis of IA, and its performance is comparable to that of the GM assay.
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