Next Article in Journal
Special Issue: Fungal Endophytes in Plants
Next Article in Special Issue
Fungal Resistance to Echinocandins and the MDR Phenomenon in Candida glabrata
Previous Article in Journal
A Solvent-Free Approach for Converting Cellulose Waste into Volatile Organic Compounds with Endophytic Fungi
Previous Article in Special Issue
Therapy of Skin, Hair and Nail Fungal Infections
Article Menu
Issue 3 (September) cover image

Export Article

Open AccessArticle
J. Fungi 2018, 4(3), 103; https://doi.org/10.3390/jof4030103

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

1
Department of Medical Microbiology, Radboud University Medical Center, 6525 Nijmegen, The Netherlands
2
Center of Expertise in Mycology Radboudumc/CWZ, 6525 Nijmegen, The Netherlands
3
Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, 6532 Nijmegen, The Netherlands
4
Department of Medical Mycology, Westerdijk Fungal Biodiversity Institute, 3584 Utrecht, The Netherlands
5
Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110021, India
*
Author to whom correspondence should be addressed.
Received: 31 July 2018 / Revised: 22 August 2018 / Accepted: 23 August 2018 / Published: 29 August 2018
(This article belongs to the Special Issue Treatments for Fungal Infections)
Full-Text   |   PDF [569 KB, uploaded 29 August 2018]   |  

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 had a voriconazole MIC above the CLSI ECV, while 28/37 (76%) isolates had an itraconazole MIC > 1 mg/L. Interestingly, only 13 of 37 (35%) isolates had a posaconazole MIC > 0.25 mg/L. View Full-Text
Keywords: cyp51A; aspergillosis; azole resistance; ECV; CLSI broth microdilution cyp51A; aspergillosis; azole resistance; ECV; CLSI broth microdilution
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Buil, J.B.; Hagen, F.; Chowdhary, A.; Verweij, P.E.; Meis, J.F. Itraconazole, Voriconazole, and Posaconazole CLSI MIC Distributions for Wild-Type and Azole-Resistant Aspergillus fumigatus Isolates. J. Fungi 2018, 4, 103.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
J. Fungi EISSN 2309-608X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top