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 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 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, 75S. 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 g/ml; itraconazole, 2 and 2 g/ml; posaconazole, 2 and 2 g/ml; and voriconazole, 64 and 32 g/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 g/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

International evaluation of CLSI MIC/MEC distributions for definition of epidemiological cutoff values (ECVs) for species of Sporothrix identified by molecular methods

VCU Med Ctr, Richmond, VA USAUniv Fed Rural Rio de Janeiro, Seropedica, BrazilInst Nacl Infectol, Fundação Oswaldo Cruz Fiocruz, Rio De Janeiro, BrazilUniv Fed Ceara, Specialized Med Mycol Ctr, Fortaleza, Ceara, BrazilPostgrad Inst Med Educ, Chandigarh, IndiaUniv Delhi, Vallabhbhai Patel Chest Inst, Delhi, IndiaCanisius Wilhelmina Hosp, Ctr Expertise Mycol, Nijmegen, NetherlandsInst Nacl Enfermedades Infecciosas Dr C, Dept Micol, Buenos Aires, DF, ArgentinaUniv Autonoma Nuevo Leon, Monterrey, MexicoNatl Inst Communicable Dis, Johannesburg, South AfricaUniv Witwatersra, Johannesburg, South AfricaPubl Hlth England, Mycol Reference Lab, Bristol, Avon, EnglandSA Pathol, Natl Mycol Reference Ctr, Adelaide, SA, AustraliaInst Nacl Infectol Evandro Chagas, Fundação Oswaldo Cruz Fiocruz, Rio De Janeiro, BrazilUniv Fed São Paulo, São Paulo, BrazilInst Biofis, São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Biofis, Rio De Janeiro, BrazilRio Claro Labs, Inst Adolfo Lutz, São Paulo, BrazilHosp Clin Dr M Quintela, Dept Lab Clin, Montevideo, UruguayHosp Gen Mexico City, Mexico City, DF, MexicoUniv Rovira & Virgili, Mycol Unit, Sch Med, Reus, SpainInst Nacl Higiene Rafael Rangel, Caracas, VenezuelaUniv Antioquia, Grp Invest Dermatol, Medellin, ColombiaUniv Adelaide, Adelaide, SA, AustraliaUniv Fed São Paulo, São Paulo, BrazilWeb of Scienc