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Updated: May 29, 2026
Broth Microdilution In Vitro Screening: An Easy and Fast Method to Detect New Antifungal Compounds
Published on: February 14, 2018
Wild-type MIC distributions and epidemiological cutoff values for amphotericin B and Aspergillus spp. for the CLSI
A Espinel-Ingroff1, M Cuenca-Estrella, A Fothergill
1VCU Medical Center, Richmond, Virginia, USA. avingrof@verizon.net
Abstract:
Although clinical breakpoints have not been established for mold testing, epidemiological cutoff values (ECVs) are available for Aspergillus spp. versus the triazoles and caspofungin. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no acquired resistance mechanisms) were defined in order to establish ECVs for six Aspergillus spp. and amphotericin B. Two sets (CLSI/EUCAST broth microdilution) of available MICs were evaluated: those for A. fumigatus (3,988/833), A. flavus (793/194), A. nidulans (184/69), A. niger (673/140), A. terreus (545/266), and A. versicolor (135/22). Three sets of data were analyzed: (i) CLSI data gathered in eight independent laboratories in Canada, Europe, and the United States; (ii) EUCAST data from a single laboratory; and (iii) the combined CLSI and EUCAST data. ECVs, expressed in μg/ml, that captured 95%, 97.5%, and 99% of the modeled wild-type population (CLSI and combined data) were as follows: for A. fumigatus, 2, 2, and 4; for A. flavus, 2, 4, and 4; for A. nidulans, 4, 4, and 4; for A. niger, 2, 2, and 2; for A. terreus, 4, 4, and 8; and for A. versicolor, 2, 2, and 2. Similar to the case for the triazoles and caspofungin, amphotericin B ECVs may aid in the detection of strains with acquired mechanisms of resistance to this agent.
Insights
Epidemiological cutoff values (ECVs) were established for amphotericin B against six Aspergillus species. These ECVs help detect antifungal resistance in mold infections, aiding clinical decisions.
Area of Science:
- Medical Mycology
- Antimicrobial Susceptibility Testing
Background:
- Clinical breakpoints are unavailable for mold antifungal testing.
- Epidemiological cutoff values (ECVs) are established for Aspergillus spp. against triazoles and caspofungin.
- Wild-type (WT) minimum inhibitory concentration (MIC) distributions are crucial for defining ECVs.
Purpose of the Study:
- To establish ECVs for six Aspergillus species against amphotericin B.
- To define wild-type MIC distributions for Aspergillus spp. and amphotericin B.
- To aid in detecting acquired resistance mechanisms to amphotericin B in Aspergillus.
Main Methods:
- Evaluated two sets of MIC data (CLSI/EUCAST broth microdilution) for six Aspergillus species.
- Analyzed three data sets: CLSI, EUCAST, and combined CLSI/EUCAST data.
- Modeled wild-type populations to determine ECVs capturing 95%, 97.5%, and 99%.
Main Results:
- ECVs for amphotericin B were determined for A. fumigatus, A. flavus, A. nidulans, A. niger, A. terreus, and A. versicolor.
- Specific ECV ranges (in μg/ml) were provided for each species at different wild-type population capture percentages.
- For example, A. fumigatus ECVs were 2, 2, and 4 μg/ml for 95%, 97.5%, and 99% WT population capture, respectively.
Conclusions:
- Established ECVs for amphotericin B against key Aspergillus species.
- These ECVs can assist in identifying Aspergillus strains with acquired resistance to amphotericin B.
- Findings complement existing ECVs for other antifungal agents, improving mold susceptibility testing.
