Itraconazole, Voriconazole, and Posaconazole CLSI MIC Distributions for Wild-Type and Azole-Resistant Aspergillus fumigatus Isolates

Journal of Fungi
Jochem B BuilJ F Meis

Abstract

Azole resistance in Aspergillus fumigatus is most frequently conferred by mutations in the cyp51A gene encoding 14α-sterol demethylases. TR34/L98H and TR46/Y121F/T289A are the two most common mutations associated with environmental resistance selection. We studied the minimal inhibitory concentration (MIC) distribution of clinical A. fumigatus isolates to characterize the Clinical and Laboratory Standards Institute (CLSI) susceptibility profiles of isolates with the wild-type (WT) cyp51A genotype, and isolates with the TR34/L98H and TR46/Y121F/T289A cyp51A mutations. Susceptibility testing was performed according to CLSI M38-A2. The MICs of 363 A. fumigatus isolates were used in this study. Based on the CLSI epidemiological cut-off values (ECVs), 141 isolates were phenotypically non-WT and 222 isolates had a phenotypically WT susceptibility. All isolates with the TR34/L98H mutation had an itraconazole MIC > 1 mg/L which is above the CLSI ECV. Eighty-six of 89 (97%) isolates with the TR34/L98H mutation had voriconazole and posaconazole MICs above the CLSI ECV, i.e., MICs of 1 and 0.25 mg/L, respectively. The isolates with a TR46/Y121F/T289A mutation showed a different phenotype. All 37 isolates with a TR46/Y121F/T289A mutation h...Continue Reading

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Citations

Jan 16, 2020·Journal of Fungi·Mireille H van der TorreRiina Rautemaa-Richardson
Jun 11, 2020·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Flavia ZendriDorina Timofte
Mar 26, 2019·Expert Opinion on Pharmacotherapy·Bryan T MogleWesley D Kufel
Apr 24, 2020·Drugs·Lu ChenRoger J M Brüggemann
Jul 14, 2020·Current Opinion in Infectious Diseases·Nathan P Wiederhold, Paul E Verweij
Dec 14, 2018·Journal of Fungi·Esther Segal, Daniel Elad
Jul 24, 2020·Current Fungal Infection Reports·Alison R NovakScott W Mueller
Oct 7, 2020·Journal of Fungi·Fatemeh AhangarkaniJacques F Meis
May 27, 2021·Studies in Mycology·A ArastehfarM Hoenigl
Jun 16, 2021·Expert Opinion on Pharmacotherapy·Shirisha Pasula, Pranatharthi H Chandrasekar
Aug 6, 2021·Diagnostic Microbiology and Infectious Disease·Michael A PfallerMariana Castanheira
Sep 8, 2021·Mycopathologia·Amelie P BrackinJohanna Rhodes

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Methods Mentioned

BETA
bronchoalveolar lavage
PCR
PCRs

Software Mentioned

AsperGenius

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Aspergillosis

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.

Aspergillosis (ASM)

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.