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Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for
A Espinel-Ingroff1, D P B Abreu2, R Almeida-Paes3
1VCU Medical Center, Richmond, Virginia, USA victoria.ingroff@vcuhealth.org.
Abstract:
Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrixschenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 μg/ml; itraconazole, 2 and 2 μg/ml; posaconazole, 2 and 2 μg/ml; and voriconazole, 64 and 32 μg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 μg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.
Insights
New epidemiologic cutoff values (ECVs) were established for common antifungal drugs against pathogenic Sporothrix species. These ECVs help identify antifungal resistance in Sporothrix schenckii and Sporothrix brasiliensis, aiding clinical treatment decisions.
Area of Science:
- Medical Mycology
- Antimicrobial Susceptibility Testing
- Infectious Diseases
Background:
- Current Clinical and Laboratory Standards Institute (CLSI) antifungal susceptibility testing conditions for Sporothrix species were based on limited data.
- Molecular identification has revealed distinct Sporothrix species, necessitating species-specific testing criteria.
- Establishing epidemiologic cutoff values (ECVs) or breakpoints (BPs) is crucial for interpreting antifungal susceptibility results.
Purpose of the Study:
- To confirm the suitability of CLSI testing conditions for various antifungal agents and Sporothrix species.
- To establish species-specific ECVs for clinically relevant, molecularly identified Sporothrix isolates.
Main Methods:
- Collected CLSI MICs/MECs data for amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin.
- Utilized data from 301 Sporothrix schenckii, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana isolates.
- Data were gathered from 17 international laboratories using standardized conidial inoculum and incubation conditions (35°C, 48–72 h).
Main Results:
- Proposed ECVs for Sporothrix schenckii and S. brasiliensis against amphotericin B (4 μg/ml), itraconazole (2 μg/ml), posaconazole (2 μg/ml), and voriconazole (64 and 32 μg/ml, respectively).
- Established ECVs for S. brasiliensis against ketoconazole (2 μg/ml) and terbinafine (0.12 μg/ml).
- Insufficient data precluded ECV calculation for ketoconazole, terbinafine, and other agents against S. schenckii, and for all agents against S. globosa and S. mexicana.
Conclusions:
- The study established species-specific ECVs for key antifungal agents against Sporothrix schenckii and Sporothrix brasiliensis.
- These ECVs can assist clinicians in identifying potentially resistant Sporothrix isolates (non-wild type) that may not respond to therapy.
- Further studies are needed to establish ECVs for other Sporothrix species and antifungal agents.
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