title: Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method.
abstract: Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C. krusei, 767 C. parapsilosis SC, 796 C. tropicalis, 1,637 Aspergillus fumigatus SC, 238 A. flavus SC, 321 A. niger SC, and 247 A. terreus SC isolates. Etest MICs from 15 laboratories (in Argentina, Europe, Mexico, South Africa, and the United States) were pooled to establish Etest ECVs. Anidulafungin, caspofungin, micafungin, and amphotericin B ECVs (in micrograms per milliliter) encompassing ≥97.5% of the statistically modeled population were 0.016, 0.5, 0.03, and 1 for C. albicans; 0.03, 1, 0.03, and 2 for C. glabrata SC; 0.06, 1, 0.25, and 4 for C. krusei; 8, 4, 2, and 2 for C. parapsilosis SC; and 0.03, 1, 0.12, and 2 for C. tropicalis The amphotericin B ECV was 0.25 μg/ml for C. dubliniensis and 2, 8, 2, and 16 μg/ml for the complexes of A. fumigatus, A. flavus, A. niger, and A. terreus, respectively. While anidulafungin Etest ECVs classified 92% of the Candida fks mutants evaluated as non-WT, the performance was lower for caspofungin (75%) and micafungin (84%) cutoffs. Finally, although anidulafungin (as an echinocandin surrogate susceptibility marker) and amphotericin B ECVs should identify Candida and Aspergillus isolates with reduced susceptibility to these agents using the Etest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.
authors: VCU Medical Center, Richmond, Virginia, USA avingrof@vcu.edu.
authors: A
authors: A
authors: Espinel-Ingroff
authors: Unit for Mycology, Statens Serum Institut, Copenhagen, Denmark, and Copenhagen University, Rigshospitalet, Copenhagen, Denmark.
authors: M
authors: M
authors: Arendrup
authors: Grupo Infección Grave, Instituto Investigación Sanitaria La Fe, Valencia, Spain.
authors: E
authors: E
authors: Cantón
authors: Instituto Nacional de Enfermedades Infecciosas Dr. C. G. Malbrán, Buenos Aires, Argentina.
authors: S
authors: S
authors: Cordoba
authors: Université Paris-Descartes, Faculté de Médecine, APHP, Hôpital Européen Georges Pompidou, Unité de Parasitologie-Mycologie, Service de Microbiologie, Paris, France.
authors: E
authors: 0000-0002-2817-3830
authors: E
authors: Dannaoui
authors: Hospital Universitario La Paz, Madrid, Spain.
authors: J
authors: J
authors: García-Rodríguez
authors: Universidad Autonóma de Nuevo León, Monterrey, Nuevo León, México.
authors: G M
authors: GM
authors: Gonzalez
authors: National Institute for Communicable Diseases, Johannesburg, South Africa.
authors: N P
authors: 0000-0001-7869-9462
authors: NP
authors: Govender
authors: Unidad de Gestion Clinica de Enfermedades Infecciosas y Microbiologia, Hospital Universitario Valme, Seville, Spain.
authors: E
authors: E
authors: Martin-Mazuelos
authors: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors: M
authors: M
authors: Lackner
authors: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors: C
authors: C
authors: Lass-Flörl
authors: Facultad de Medicina, Universidad de Córdoba, H. U. Reina Sofía, Córdoba, Spain.
authors: M J
authors: MJ
authors: Linares Sicilia
authors: Hospital Universitario Puerta del Mar, Cádiz, Spain.
authors: M A
authors: MA
authors: Rodriguez-Iglesias
authors: Servicio de Microbiología, Hospital Universitario Central de Asturias, Asturias, Spain.
authors: T
authors: T
authors: Pelaez
authors: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors: R K
authors: RK
authors: Shields
authors: Laboratorio de Micología y Diagnóstico Molecular-Facultad de Bioquímica y Ciencias Biológicas-Universidad Nacional del Litoral, Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), CCT, Santa Fe, Argentina.
authors: G
authors: G
authors: Garcia-Effron
authors: Servicio de Microbiología Clínica y Enfermedades Infecciosas-VIH, Hospital General Universitario Gregorio Marañon, and Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors: J
authors: 0000-0002-7901-8355
authors: J
authors: Guinea
authors: Institute of Microbiology and Institute of Hygiene, Universita Cattolica del Sacro Cuore, Rome, Italy.
authors: M
authors: M
authors: Sanguinetti
authors: University of Adelaide, Adelaide, Australia.
authors: J
authors: J
authors: Turnidge
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D002175:Candida / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D052978:Disk Diffusion Antimicrobial Tests; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology*; D005060:Europe; D007843:Latin America; D013019:South Africa; D014481:United States
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D000666:Amphotericin B
keywords: ECVs; Etest ECVs; Etest MICs Aspergillus; Etest MICs Candida; WT isolates; amphotericin B resistance; antifungal resistance; echinocandin resistance; non-WT; susceptibility marker