Background: Nakaseomyces glabrata, formerly Candida glabrata, is an opportunistic yeast and an emerging cause of human infections. The use of broth microdilution (BMD) methodologies for caspofungin (CSP) antifungal susceptibility testing (AFST) against N. glabrata is reported to be prone to high inter-laboratory variation. We aimed to compare CSP minimum inhibitory concentrations (MICs) of N. glabrata isolates from our institution with those obtained by the Reference Laboratory for the same isolates. Methods: All clinically significant N. glabrata isolates from 2019-2021 inclusive were reviewed. AFST was performed locally using the VITEK2 system with the AST-YS08 card while E-tests were performed at Mycology Reference Laboratory (MRL), and agreement between these two methods was evaluated – categorical and essential. Results: 41 isolates were reviewed during the study period – 30 from blood cultures, seven from intra-operative theatre specimens and four from sterile site drain fluids. Despite an essential agreement of 100% within ±2 log2 dilution, marked discrepancies were noted in interpretative breakpoints between assays with 17 Minor and 16 Major category errors. Categorical agreement was 19.5%, with the VITEK2 over-estimating resistance. A Mann-Whitney U Test assessed the relationship of MICs across the AFST modalities, and a statistically significant difference was noted, p<0.01, with a higher mean rank for VITKEK2 outputs. Conclusion: While the VITEK2 system is highly applicable, its performance for CSP AFST is unreliable and potentially results in the mis-classification of susceptible isolates as highlighted in our study. The use of VITEK2 AST-YS08 micafungin as a sentinel echinocandin should be explored and/or the evaluation of CSP-specific E-tests as utilised by the MRL. These methods appear more consistent and less prone to the variation seen with BMD for CSP.
Background: The use of automated broth-microdilution systems for caspofungin antifungal susceptibility testing (AST) for Nakaseomyces glabrata is prone to high inter-laboratory variation. We aim to review caspofungin minimum inhibitory concentrations (MICs) of clinically significant N.glabrata isolates, as reported locally and compare with reference laboratory results for the same isolate. Methods: All clinically significant N.glabrata isolates from 2019-2021 inclusive were reviewed. Caspofungin MICs were obtained locally using the VITEK2 system and strains were referred to the Mycology Reference Laboratory for confirmatory testing via E-Tests. MICs were compared using categorical and essential agreement. Results: Of the forty-one isolates reviewed, marked discrepancies were noted in interpretative breakpoints between assays, producing 16 Minor and Major Category Errors. Categorical agreement was found to be 22%, with the VITEK2 over-estimating resistance. Doubling dilution differences revealed an essential agreement of 61% within ±1 log2 dilution. Conclusion: Performing caspofungin AST using broth-microdilution methods is prone to high inter-laboratory variation, and potentially results in the mis-classification of susceptible isolates as highlighted in our study. The use of E-tests has been shown to be highly reliable and not prone to inter-laboratory variation. It may be worthwhile looking into adopting a similar testing approach locally from an economic and patient-centred view.
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