Comparison of Two Commercial Colorimetric Broth Microdilution Tests for Candida Susceptibility Testing: Sensititre YeastOne versus MICRONAUT-AM

Abstract

Two colorimetric broth microdilution antifungal susceptibility tests were compared, Sensititre YeastOne and MICRONAUT-AM for nine antifungal agents. One hundred clinical Candida isolates were tested, representing a realistic population for susceptibility testing in daily practice. The reproducibility characteristics were comparable. Only for fluconazole, caspofungin, 5-flucytosine and amphotericin B, an essential agreement of ≥90% could be demonstrated. Sensititre minimal inhibitory concentrations (MICs) were systematically higher than MICRONAUT MICs for all antifungals, except for itraconazole. CLSI clinical breakpoints (CBPs) and epidemiological cut-off values (ECVs) were used for Sensititre MICs while for MICRONAUT the EUCAST CBPs and ECVs were used. Only fluconazole, micafungin, and amphotericin B had a categorical agreement of ≥90%. For fluconazole, micafungin, and amphotericin B the susceptibility proportions were comparable. Susceptibility proportion of posaconazole and voriconazole was higher using the MICRONAUT system. For itraconazole and anidulafungin, the susceptibility proportion was higher using Sensititre. It was not possible to determine the true MIC values or the correctness of a S/I/R result since both commercial systems were validated against a different reference method. These findings show that there is a significant variability in susceptibility pattern and consequently on use of antifungals in daily practice, depending on the choice of commercial system.

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“…In contrast, our MODAL MICs obtained with MN or MNV were more than 1 dilution apart for anidulafungin with C. krusei and posaconazole, voriconazole, and candins with C. parapsilosis than those described by EUCAST. These data were close to those reported by Philips et al. (2021) .…”

“…Amphotericin B could be compared only based on ECV/ECOFF, since CLSI does not provide breakpoints for this drug. Our analysis also highlighted the discrepancies between the two methods with specific drugs such as anidulafungin and micafungin as described by Philips et al. (2021) , who identified 21% of the MEs attributable to anidulafungin when comparing YO and MNV raw MICs.…”

“…We observed that in strains harboring mutations, the elevation of MIC was more pronounced with YO using CLSI criteria than with MNV, using EUCAST criteria. Indeed, previous studies already observed that CLSI MIC has a tendency to be higher than the EUCAST for more drugs and species ( Pfaller et al., 2014 ; Philips et al., 2021 ). ( Philips et al., 2021 ), and in contrast to ( Pfaller et al., 2014 ), we observed that this difference was also true for caspofungin at least for the C. glabrata isolates analyzed.…”

“…For each strain–antifungal agent combination, the modal MIC was defined. The reproducibility is defined, as described before ( Philips et al., 2021 ), as the percentage of MICs within the modal MIC +/- one dilution, meaning on a 3-dilution range. When the modal MIC consists of two adjacent dilutions, for example, 0.125 and 0.25 mg/L, the reproducibility is defined as the percentage of MICs within a 4-dilution range, so from 0.0625 to 0.5 mg/L for the example given.…”

“…However, both reference methods are labor intensive, making them difficult to be implemented in a routine laboratory. In contrast, commercial methods offer a simpler and easy-to- implement alternative ( Lombardi et al., 2004 ; Kritikos et al., 2018 ; Philips et al., 2021 ). The Sensititre™ YeastOne™, AFST (Thermo Fisher Scientific, Waltham, MA, United States) follows the CLSI protocol and interpretations, whereas the MICRONAUT-AM Antifungal Agents MIC (MERLIN Gesellschaft fuer mikrobiologische Diagnostika GmbH, Bornheim, Germany) is an adapted protocol of the EUCAST protocol and is interpreted with its criteria.…”