title: Wild-type MIC distributions and epidemiological cutoff values for amphotericin B, flucytosine, and itraconazole and Candida spp. as determined by CLSI broth microdilution.
abstract: Clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs) have been established for several Candida spp. and the newer triazoles and echinocandins but are not yet available for older antifungal agents, such as amphotericin B, flucytosine, or itraconazole. We determined species-specific ECVs for amphotericin B (AMB), flucytosine (FC) and itraconazole (ITR) for eight Candida spp. (30,221 strains) using isolates from 16 different laboratories in Brazil, Canada, Europe, and the United States, all tested by the CLSI reference microdilution method. The calculated 24- and 48-h ECVs expressed in μg/ml (and the percentages of isolates that had MICs less than or equal to the ECV) for AMB, FC, and ITR, respectively, were 2 (99.8)/2 (99.2), 0.5 (94.2)/1 (91.4), and 0.12 (95.0)/0.12 (92.9) for C. albicans; 2 (99.6)/2 (98.7), 0.5 (98.0)/0.5 (97.5), and 2 (95.2)/4 (93.5) for C. glabrata; 2 (99.7)/2 (97.3), 0.5 (98.7)/0.5 (97.8), and 05. (99.7)/0.5 (98.5) for C. parapsilosis; 2 (99.8)/2 (99.2), 0.5 (93.0)/1 (90.5), and 0.5 (97.8)/0.5 (93.9) for C. tropicalis; 2 (99.3)/4 (100.0), 32 (99.4)/32 (99.3), and 1 (99.0)/2 (100.0) for C. krusei; 2 (100.0)/4 (100.0), 0.5 (95.3)/1 (92.9), and 0.5 (95.8)/0.5 (98.1) for C. lusitaniae; -/2 (100.0), 0.5 (98.8)/0.5 (97.7), and 0.25 (97.6)/0.25 (96.9) for C. dubliniensis; and 2 (100.0)/2 (100.0), 1 (92.7)/-, and 1 (100.0)/2 (100.0) for C. guilliermondii. In the absence of species-specific CBP values, these wild-type (WT) MIC distributions and ECVs will be useful for monitoring the emergence of reduced susceptibility to these well-established antifungal agents.
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA. michael-pfaller@jmilabs.com
authors.forename: M A
authors.initials: MA
authors.lastname: Pfaller
authors.forename: A
authors.initials: A
authors.lastname: Espinel-Ingroff
authors.forename: E
authors.initials: E
authors.lastname: Canton
authors.forename: M
authors.initials: M
authors.lastname: Castanheira
authors.forename: M
authors.initials: M
authors.lastname: Cuenca-Estrella
authors.forename: D J
authors.initials: DJ
authors.lastname: Diekema
authors.forename: A
authors.initials: A
authors.lastname: Fothergill
authors.forename: J
authors.initials: J
authors.lastname: Fuller
authors.forename: M
authors.initials: M
authors.lastname: Ghannoum
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: S R
authors.initials: SR
authors.lastname: Lockhart
authors.forename: E
authors.initials: E
authors.lastname: Martin-Mazuelos
authors.forename: M S C
authors.initials: MS
authors.lastname: Melhem
authors.forename: L
authors.initials: L
authors.lastname: Ostrosky-Zeichner
authors.forename: P
authors.initials: P
authors.lastname: Pappas
authors.forename: T
authors.initials: T
authors.lastname: Pelaez
authors.forename: J
authors.initials: J
authors.lastname: Peman
authors.forename: J
authors.initials: J
authors.lastname: Rex
authors.forename: M W
authors.initials: MW
authors.lastname: Szeszs
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001938:Brazil; D002170:Canada; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology*; D005060:Europe; D005437:Flucytosine / Q000494:pharmacology*; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000592:standards; D014481:United States
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D000666:Amphotericin B; D005437:Flucytosine