Abstract

Antifungal susceptibility testing (AFST) of clinical isolates is a tool in routine diagnostics to facilitate decision making on optimal antifungal therapy. The minimal inhibitory concentration (MIC)-phenomena (trailing and paradoxical effects (PXE)) observed in AFST complicate the unambiguous and reproducible determination of MICs and the impact of these phenomena on in vivo outcome are not fully understood. We aimed to link the MIC-phenomena with in vivo treatment response using the alternative infection model Galleria mellonella. We found that Candida albicans strains exhibiting PXE for caspofungin (CAS) had variable treatment outcomes in the Galleria model. In contrast, C. albicans strains showing trailing for voriconazole failed to respond in vivo. Caspofungin- and voriconazole-susceptible C. albicans strains responded to the respective antifungal therapy in vivo. In conclusion, MIC data and subsequent susceptibility interpretation of strains exhibiting PXE and/or trailing should be carried out with caution, as both effects are linked to drug adaptation and treatment response is uncertain to predict.

Highlights

  • In times of rising numbers of multi-drug resistant microorganisms, antifungal susceptibility testing (AFST) is an important tool in routine diagnostics to target antifungal therapy

  • The minimal inhibitory concentrations (MICs) measured for a clinical isolate and subsequent interpretation of the susceptibility based on the clinical breakpoints (CBPs) is one key factor for choosing the most effective therapeutic approach

  • 203 clinical isolates obtained from patients suffering from invasive candidiasis caused by Candida albicans were studied during a one year-period at the Division of Hygiene and Medical

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Summary

Introduction

In times of rising numbers of multi-drug resistant microorganisms, antifungal susceptibility testing (AFST) is an important tool in routine diagnostics to target antifungal therapy. The result of AFST is an antifungal susceptibility profile for the clinical isolate and all systemic antifungal agents. The minimal inhibitory concentrations (MICs) measured for a clinical isolate and subsequent interpretation of the susceptibility based on the clinical breakpoints (CBPs) is one key factor for choosing the most effective therapeutic approach. The two internationally accepted standard AFST methods are EUCAST [2] and CLSI [3]. They allow the categorization of isolates as susceptible, intermediate, or resistant [4] and AFST according to these guidelines has become standard procedure to guide antifungal therapy [5]

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