Reviewer response for version 1

Abstract

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.