Molecular Tools for the Detection and Deduction of Azole Antifungal Drug Resistance Phenotypes in Aspergillus Species.

Anna Dudakova, Birgit Spiess, Marut Tangwattanachuleeporn, Christoph Sasse, Dieter Buchheidt, Michael Weig, Uwe Groß, Oliver Bader

Journal: Clinical microbiology reviews 2017;30(4):1065-1091

PMID: 28903985

Abstract

The incidence of azole resistance in species has increased over the past years, most importantly for . This is partially attributable to the global spread of only a few resistance alleles through the environment. Secondary resistance is a significant clinical concern, as invasive aspergillosis with drug-susceptible strains is already difficult to treat, and exclusion of azole-based antifungals from prophylaxis or first-line treatment of invasive aspergillosis in high-risk patients would dramatically limit drug choices, thus increasing mortality rates for immunocompromised patients. Management options for invasive aspergillosis caused by azole-resistant strains were recently reevaluated by an international expert panel, which concluded that drug resistance testing of cultured isolates is highly indicated when antifungal therapy is intended. In geographical regions with a high environmental prevalence of azole-resistant strains, initial therapy should be guided by such analyses. More environmental and clinical screening studies are therefore needed to generate the local epidemiologic data if such measures are to be implemented on a sound basis. Here we propose a first workflow for evaluating isolates from screening studies, and we compile the MIC values correlating with individual amino acid substitutions in the products of genes for interpretation of DNA sequencing data, especially in the absence of cultured isolates.

Copyright © 2017 American Society for Microbiology.

Address: Institute for Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany.; 3rd Department of Internal Medicine, Hematology and Oncology, Mannheim University Hospital, University of Heidelberg, Mannheim, Germany.; Unit of Medical Technology, Faculty of Allied Health Sciences, Burapha University, Chon Buri, Thailand.; Institute of Microbiology and Genetics, Department of Molecular Microbiology & Genetics, Georg August Universität Göttingen, Göttingen, Germany.; Institute for Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany [email protected].
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