title: Clinical breakpoints for voriconazole and Candida spp. revisited: review of microbiologic, molecular, pharmacodynamic, and clinical data as they pertain to the development of species-specific interpretive criteria.
abstract: We reassessed the Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) for voriconazole. We examined i) the essential (EA: ±2 dilutions) and categorical agreement between 24-h CLSI and EUCAST methods for voriconazole testing of Candida, ii) wild-type (WT) MICs and epidemiologic cutoff values (ECVs) for voriconazole by both CLSI and EUCAST methods, and iii) correlation of MICs with outcomes from previously published data using CLSI methods. We applied these findings to propose new 24-h species-specific CLSI CBPs. Adjusted 24-h CBPs for voriconazole and C. albicans, C. tropicalis, and C. parapsilosis (susceptible, ≤ 0.125 μg/mL; intermediate, 0.25-0.5 μg/mL; resistant, ≥ 1 μg/mL) should be more sensitive for detecting emerging resistance among common Candida species and provide consistency with EUCAST CBPs. In the absence of CBPs for voriconazole and C. glabrata (and less common species), we recommend that their respective ECVs be used to detect the emergence of non-WT strains.
authors.affiliation: University of Iowa Carver College of Medicine, Iowa City, IA 52246, USA. michael-pfaller@uiowa.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pfaller
authors.forename: David
authors.initials: D
authors.lastname: Andes
authors.forename: Maiken C
authors.initials: MC
authors.lastname: Arendrup
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Diekema
authors.forename: Ana
authors.initials: A
authors.lastname: Espinel-Ingroff
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Alexander
authors.forename: Steven D
authors.initials: SD
authors.lastname: Brown
authors.forename: Vishnu
authors.initials: V
authors.lastname: Chaturvedi
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Fowler
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Ghannoum
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Johnson
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Knapp
authors.forename: Mary R
authors.initials: MR
authors.lastname: Motyl
authors.forename: Luis
authors.initials: L
authors.lastname: Ostrosky-Zeichner
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole