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Updated: Jun 3, 2026
Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Wild-type MIC distributions and epidemiological cutoff values for caspofungin and Aspergillus spp. for the CLSI broth
A Espinel-Ingroff1, A Fothergill, J Fuller
1VCU Medical Center, 3804 Dover Rd., Richmond, VA 23221, USA. avingrof@verizon.net
Abstract:
Clinical breakpoints have not been established for mold testing. Epidemiologic cutoff values (ECVs) are available for six Aspergillus spp. and the triazoles, but not for caspofungin. Wild-type (WT) minimal effective concentration (MEC) distributions (organisms in a species-drug combination with no acquired resistance mechanisms) were defined in order to establish ECVs for six Aspergillus spp. and caspofungin. The number of available isolates was as follows: 1,691 A. fumigatus, 432 A. flavus, 192 A. nidulans, 440 A. niger, 385 A. terreus, and 75 A. versicolor isolates. CLSI broth microdilution MEC data gathered in five independent laboratories in Canada, Europe, and the United States were aggregated for the analyses. ECVs expressed in μg/ml that captured 95% and 99% of the modeled wild-type population were for A. fumigatus 0.5 and 1, A. flavus 0.25 and 0.5, A. nidulans 0.5 and 0.5, A. niger 0.25 and 0.25, A. terreus 0.25 and 0.5, and A. versicolor 0.25 and 0.5. Although caspofungin ECVs are not designed to predict the outcome of therapy, they may aid in the detection of strains with reduced antifungal susceptibility to this agent and acquired resistance mechanisms.
Insights
New epidemiologic cutoff values (ECVs) were established for caspofungin against six Aspergillus species. These values aid in detecting Aspergillus strains with reduced susceptibility to caspofungin, an important antifungal agent.
Area of Science:
- Medical Mycology
- Antimicrobial Susceptibility Testing
- Clinical Microbiology
Background:
- Clinical breakpoints are lacking for mold antifungal testing.
- Epidemiologic cutoff values (ECVs) exist for Aspergillus spp. and triazoles, but not for caspofungin.
- Defining wild-type (WT) minimal effective concentration (MEC) distributions is crucial for establishing ECVs.
Purpose of the Study:
- To establish ECVs for caspofungin against six Aspergillus species.
- To define wild-type (WT) MEC distributions for these Aspergillus species.
- To provide a tool for detecting reduced antifungal susceptibility to caspofungin.
Main Methods:
- Aggregated CLSI broth microdilution MEC data from five international laboratories.
- Analyzed MEC data from 1,691 A. fumigatus, 432 A. flavus, 192 A. nidulans, 440 A. niger, 385 A. terreus, and 75 A. versicolor isolates.
- Modeled WT populations to determine ECVs capturing 95% and 99% of isolates.
Main Results:
- Established caspofungin ECVs (μg/ml) for six Aspergillus spp.: A. fumigatus (0.5/1), A. flavus (0.25/0.5), A. nidulans (0.5/0.5), A. niger (0.25/0.25), A. terreus (0.25/0.5), and A. versicolor (0.25/0.5) for 95%/99% WT populations.
- ECVs varied among the Aspergillus species tested.
- The data provide a basis for identifying potential resistance mechanisms.
Conclusions:
- Established caspofungin ECVs for six Aspergillus species, aiding in the detection of strains with reduced susceptibility.
- These ECVs are valuable for monitoring antifungal resistance in Aspergillus.
- While not predicting therapy outcomes, ECVs assist in identifying Aspergillus isolates with potential acquired resistance to caspofungin.
