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

Abstract

Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic <i>Sporothrix</i> species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of <i>Sporothrix</i><i>schenckii sensu lato</i> 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 <i>Sporothrix</i> 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 <i>Sporothrix schenckii sensu stricto</i>, 486 <i>S. brasiliensis</i>, 75 <i>S. globosa</i>, and 13 <i>S. mexicana</i> 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 <i>S. schenckii</i> and <i>S. brasiliensis</i>, 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 <i>S. brasiliensis</i> 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 <i>S. schenckii</i>, as well as ECVs for <i>S. globosa</i> and <i>S. mexicana</i> These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.