Multicenter and international study of MIC/MEC distributions for definition of epidemiological cutoff values (ECVs) for species of Sporothrix identified by molecular methods

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 Sporothrix schenckii 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 these species. We collected available CLSI MICs/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, South and North America) using conidial inoculum suspensions and 48-72 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 ECVs for S. schenckii as well as ECVs for S. globosa and S. mexicana or any other antifungal agent. These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.