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Updated: Jun 11, 2026
Isolation of Culturable Yeasts and Molds from Soils to Investigate Fungal Population Structure
Published on: May 27, 2022
Wild-type MIC distributions and epidemiological cutoff values for the triazoles and six Aspergillus spp. for the CLSI
A Espinel-Ingroff1, D J Diekema, A Fothergill
1VCU Medical Center, 3804 Dover Rd., Richmond, VA 23221, USA. avingrof@vcu.edu
Abstract:
Clinical breakpoints have not been established for mold testing. Wild-type (WT) MIC distributions (organisms in a species/drug combination with no detectable acquired resistance mechanisms) were defined in order to establish epidemiologic cutoff values (ECVs) for five Aspergillus spp. and itraconazole, posaconazole, and voriconazole. Also, we have expanded prior ECV data for Aspergillus fumigatus. The number of available isolates varied according to the species/triazole combination as follows: 1,684 to 2,815 for A. fumigatus, 323 to 592 for A. flavus, 131 to 143 for A. nidulans, 366 to 520 for A. niger, 330 to 462 for A. terreus, and 45 to 84 for A. versicolor. CLSI broth microdilution MIC data gathered in five independent laboratories in Europe and the United States were aggregated for the analyses. ECVs expressed in microg/ml were as follows (percentages of isolates for which MICs were equal to or less than the ECV are in parentheses): A. fumigatus, itraconazole, 1 (98.8%); posaconazole, 0.5 (99.2%); voriconazole, 1 (97.7%); A. flavus, itraconazole, 1 (99.6%); posaconazole, 0.25 (95%); voriconazole, 1 (98.1%); A. nidulans, itraconazole, 1 (95%); posaconazole, 1 (97.7%); voriconazole, 2 (99.3%); A. niger, itraconazole, 2 (100%); posaconazole, 0.5 (96.9%); voriconazole, 2 (99.4%); A. terreus, itraconazole, 1 (100%); posaconazole, 0.5 (99.7%); voriconazole, 1 (99.1%); A. versicolor, itraconazole, 2 (100%); posaconazole, 1 (not applicable); voriconazole, 2 (97.5%). Although ECVs do not predict therapy outcome as clinical breakpoints do, they may aid in detection of azole resistance (non-WT MIC) due to cyp51A mutations, a resistance mechanism in some Aspergillus spp. These ECVs should be considered for inclusion in the future CLSI M38-A2 document revision.
Insights
This study defines epidemiologic cutoff values (ECVs) for five Aspergillus species against key antifungal drugs, aiding in the detection of azole resistance. These ECVs are crucial for monitoring antifungal drug resistance in mold infections.
Area of Science:
- Mycology
- Clinical Microbiology
- Antimicrobial Resistance
Background:
- Clinical breakpoints for mold antifungal susceptibility testing are not established.
- Wild-type (WT) Minimum Inhibitory Concentration (MIC) distributions are essential for defining epidemiologic cutoff values (ECVs).
- Azole antifungal resistance, often mediated by cyp51A mutations, is a growing concern in Aspergillus infections.
Purpose of the Study:
- To establish epidemiologic cutoff values (ECVs) for five Aspergillus species (A. fumigatus, A. flavus, A. nidulans, A. niger, A. terreus, A. versicolor) against itraconazole, posaconazole, and voriconazole.
- To expand existing ECV data for Aspergillus fumigatus.
- To provide a basis for detecting azole resistance in Aspergillus species.
Main Methods:
- Aggregated CLSI broth microdilution MIC data from five independent laboratories in Europe and the United States.
- Analyzed WT MIC distributions for various Aspergillus species and triazole antifungal agents.
- Calculated ECVs in microg/ml for each species/drug combination.
Main Results:
- Established ECVs for itraconazole, posaconazole, and voriconazole across five Aspergillus species, with specific values provided for each combination.
- Expanded ECV data for A. fumigatus, including MIC distributions for 1,684 to 2,815 isolates.
- Reported high percentages of isolates with MICs at or below the ECVs, indicating a predominantly wild-type population for most combinations.
Conclusions:
- The established ECVs can aid in the detection of azole resistance (non-WT MIC) in Aspergillus species, particularly those with cyp51A mutations.
- While ECVs do not predict therapy outcomes like clinical breakpoints, they serve as valuable tools for epidemiological surveillance.
- These ECVs are recommended for consideration in future revisions of the CLSI M38-A2 document.
