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Published on: February 14, 2018
International Evaluation of MIC Distributions and Epidemiological Cutoff Value (ECV) Definitions for Fusarium Species
A Espinel-Ingroff1, A L Colombo2, S Cordoba3
1VCU Medical Center, Richmond, Virginia, USA avingrof@vcu.edu.
Abstract:
The CLSI epidemiological cutoff values (ECVs) of antifungal agents are available for various Candida spp., Aspergillus spp., and the Mucorales. However, those categorical endpoints have not been established for Fusarium spp., mostly due to the difficulties associated with collecting sufficient CLSI MICs for clinical isolates identified according to the currently recommended molecular DNA-PCR-based identification methodologies. CLSI MIC distributions were established for 53 Fusarium dimerum species complex (SC), 10 F. fujikuroi, 82 F. proliferatum, 20 F. incarnatum-F. equiseti SC, 226 F. oxysporum SC, 608 F. solani SC, and 151 F. verticillioides isolates originating in 17 laboratories (in Argentina, Australia, Brazil, Canada, Europe, Mexico, and the United States). According to the CLSI guidelines for ECV setting, ECVs encompassing ≥97.5% of pooled statistically modeled MIC distributions were as follows: for amphotericin B, 4 μg/ml (F. verticillioides) and 8 μg/ml (F. oxysporum SC and F. solani SC); for posaconazole, 2 μg/ml (F. verticillioides), 8 μg/ml (F. oxysporum SC), and 32 μg/ml (F. solani SC); for voriconazole, 4 μg/ml (F. verticillioides), 16 μg/ml (F. oxysporum SC), and 32 μg/ml (F. solani SC); and for itraconazole, 32 μg/ml (F. oxysporum SC and F. solani SC). Insufficient data precluded ECV definition for the other species. Although these ECVs could aid in detecting non-wild-type isolates with reduced susceptibility to the agents evaluated, the relationship between molecular mechanisms of resistance (gene mutations) and MICs still needs to be investigated for Fusarium spp.
Insights
New epidemiological cutoff values (ECVs) for antifungal agents were established for Fusarium species, aiding in the detection of resistant fungal infections. Further research is needed to link these ECVs with specific resistance mechanisms in Fusarium.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Clinical Microbiology
Background:
- Epidemiological cutoff values (ECVs) guide antifungal susceptibility testing for clinical isolates.
- Established ECVs exist for Candida, Aspergillus, and Mucorales, but not for Fusarium species.
- Challenges in Fusarium identification and limited MIC data have hindered ECV development.
Purpose of the Study:
- To establish CLSI-based ECVs for various antifungal agents against clinically relevant Fusarium species.
- To provide a basis for detecting non-wild-type Fusarium isolates with reduced antifungal susceptibility.
Main Methods:
- Collected CLSI MIC data for multiple Fusarium species complexes and species from 17 international laboratories.
- Utilized CLSI guidelines for setting ECVs based on statistically modeled MIC distributions (≥97.5%).
Main Results:
- ECVs were defined for amphotericin B, posaconazole, voriconazole, and itraconazole against F. verticillioides, F. oxysporum SC, and F. solani SC.
- Specific ECV ranges were determined for each drug-fungus combination, e.g., posaconazole ECV of 8 μg/ml for F. oxysporum SC.
- Insufficient data prevented ECV definition for other Fusarium species and antifungal agents.
Conclusions:
- The established ECVs can assist in identifying Fusarium isolates with potentially reduced susceptibility to tested antifungals.
- Further investigation is required to correlate molecular resistance mechanisms (gene mutations) with observed MICs in Fusarium species.
