title: Interlaboratory variability of Caspofungin MICs for Candida spp. Using CLSI and EUCAST methods: should the clinical laboratory be testing this agent?
abstract: Although Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for Candida spp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550 Candida isolates from 17 laboratories (Brazil, Canada, Europe, Mexico, Peru, and the United States), we observed an extraordinary amount of modal variability (wide ranges) among laboratories as well as truncated and bimodal MIC distributions. The species-specific modes across different laboratories ranged from 0.016 to 0.5 μg/ml for C. albicans and C. tropicalis, 0.031 to 0.5 μg/ml for C. glabrata, and 0.063 to 1 μg/ml for C. krusei. Variability was also similar among MIC distributions for C. dubliniensis and C. lusitaniae. The exceptions were C. parapsilosis and C. guilliermondii MIC distributions, where most modes were within one 2-fold dilution of each other. These findings were consistent with available data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (403 to 2,556 MICs) for C. albicans, C. glabrata, C. krusei, and C. tropicalis. Although many factors (caspofungin powder source, stock solution solvent, powder storage time length and temperature, and MIC determination testing parameters) were examined as a potential cause of such unprecedented variability, a single specific cause was not identified. Therefore, it seems highly likely that the use of the CLSI species-specific caspofungin CBPs could lead to reporting an excessive number of wild-type (WT) isolates (e.g., C. glabrata and C. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for Candida is not recommended; micafungin or anidulafungin data could be used instead.
authors.affiliation: Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
authors.forename: A
authors.initials: A
authors.lastname: Espinel-Ingroff
authors.forename: M C
authors.initials: MC
authors.lastname: Arendrup
authors.forename: M A
authors.initials: MA
authors.lastname: Pfaller
authors.forename: L X
authors.initials: LX
authors.lastname: Bonfietti
authors.forename: B
authors.initials: B
authors.lastname: Bustamante
authors.forename: E
authors.initials: E
authors.lastname: Canton
authors.forename: E
authors.initials: E
authors.lastname: Chryssanthou
authors.forename: M
authors.initials: M
authors.lastname: Cuenca-Estrella
authors.forename: E
authors.initials: E
authors.lastname: Dannaoui
authors.forename: A
authors.initials: A
authors.lastname: Fothergill
authors.forename: J
authors.initials: J
authors.lastname: Fuller
authors.forename: P
authors.initials: P
authors.lastname: Gaustad
authors.forename: G M
authors.initials: GM
authors.lastname: Gonzalez
authors.forename: J
authors.initials: J
authors.lastname: Guarro
authors.forename: C
authors.initials: C
authors.lastname: Lass-Flörl
authors.forename: S R
authors.initials: SR
authors.lastname: Lockhart
authors.forename: J F
authors.initials: JF
authors.lastname: Meis
authors.forename: C B
authors.initials: CB
authors.lastname: Moore
authors.forename: L
authors.initials: L
authors.lastname: Ostrosky-Zeichner
authors.forename: T
authors.initials: T
authors.lastname: Pelaez
authors.forename: S R B S
authors.initials: SR
authors.lastname: Pukinskas
authors.forename: G
authors.initials: G
authors.lastname: St-Germain
authors.forename: M W
authors.initials: MW
authors.lastname: Szeszs
authors.forename: J
authors.initials: J
authors.lastname: Turnidge
mesh_terms: D000077612:Anidulafungin; D000935:Antifungal Agents / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D000077336:Caspofungin; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000627:therapeutic use*; D005060:Europe; D006801:Humans; D055666:Lipopeptides / Q000627:therapeutic use; D000077551:Micafungin; D008826:Microbial Sensitivity Tests / Q000592:standards / Q000706:statistics & numerical data; D009656:North America; D015588:Observer Variation; D013020:South America; D013045:Species Specificity
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077612:Anidulafungin; D000077336:Caspofungin; D000077551:Micafungin
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