Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods

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 tam 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 MICsiminimal effective concentrations (MECs) of amphotericin B. five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu strict, 486 S. brosiliensis, 75 S. globes, 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 degrees C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasifiensis, respectively: amphotericin B, 4 and 4 mu g/m.; itraconazole, 2 and 2 mu g/ml, posaconazole, 2 and 2 mu g/ml; and voriconazole, 64 and 32 mu g/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 mu g/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any