Challenges and progressions in antifungal susceptibility testing

Abstract number: 1732_251

Arikan S.

Development of standard antifungal susceptibility testing (AFST) assays has been one of the most important progressions in the field of medical mycology. CLSI (Clinical and Laboratory Standards Institute) microdilution and disk diffusion methods as well as AFST-EUCAST (European Committee for Antimicrobial Susceptibility Testing – Antifungal Susceptibility Testing Subcommittee) microdilution reference methodology are the currently used standard assays. Recent progressions have further expanded the knowledge on application and clinical utility of AFST. Among these are validation of the previously documented CLSI fluconazole MIC breakpoints and dose-dependent susceptibility concept for fluconazole vs. Candida, and documentation of MIC breakpoints and disk diffusion inhibition zone interpretive parameters for voriconazole vs. Candida. The use of fluconazole susceptibility profile as a surrogate marker for prediction of voriconazole susceptibility has also been proposed recently. In addition, based on the modifications of the CLSI M38-A reference method, new guidelines for in vitro susceptibility testing of antifungal agents against Aspergillus spp. have been developed by AFST-EUCAST. A standard assay for testing antifungal agents against dermatophytes is also under development. Further investigations address the applicability of other methods, which are more practical and/or require shorter incubation periods. Among these are Etest, colorimetric methods, flow cytometry, and ergosterol quantitation. Utility of flow cytometry for AFST of yeasts and moulds is being currently studied and appears promising. Assessment of metabolic activity by using XTT colorimetric assay is also being investigated as a novel approach, particularly for determination of quantitative endpoints for testing caspofungin against Aspergillus, and for susceptibility testing of Zygomycetes. Despite these progressions, utility of AFST in direction of antifungal therapy and prediction of clinical outcome is still limited. While in vitro triazole (particularly fluconazole) susceptibility results for Candida appear to be optimally correlated with clinical outcome, data are either limited and investigational or fail to demonstrate any significant in vitro–in vivo correlation for most of the remaining fungus–antifungal drug combinations. Importantly and conclusively, the results obtained by AFST constitute one of the several factors that influence clinical outcome. Optimisation of test methodologies and parameters for routine use and expanded in vitro-in vivo correlation studies may further enhance the role of AFST as an adjunct in direction of antifungal therapy.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
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