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Deciphering Candida auris Paradoxical Growth Effect (Eagle Effect) in Response to Echinocandins
Milena Kordalewska1, David S Perlin2
1Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA. milena.kordalewska@hmh-cdi.org.
Abstract:
The paradoxical growth effect (PGE; also known as Eagle effect) is an in vitro phenomenon observed during antifungal susceptibility testing (AFST). In PGE, some fungal isolates grow in medium containing high concentrations of an echinocandin, above the minimal inhibitory concentration (MIC), despite being fully susceptible at lower concentrations. The presence of PGE complicates the assignment of isolates to susceptible or resistant category, especially in the case of newly emerged pathogens like Candida auris, for which susceptibility breakpoints are not established.Here we describe a protocol aiding in the determination of whether a given C. auris isolate is echinocandin-resistant or echinocandin-susceptible but exhibiting paradoxical growth.
Insights
The paradoxical growth effect (PGE) causes some fungi to grow at high antifungal drug levels. This protocol helps distinguish true resistance from PGE in Candida auris.
Area of Science:
- Mycology
- Antifungal Drug Discovery
- Clinical Microbiology
Background:
- The paradoxical growth effect (PGE), or Eagle effect, is an in vitro phenomenon in antifungal susceptibility testing (AFST).
- PGE involves fungal isolates growing at echinocandin concentrations above the minimal inhibitory concentration (MIC), despite susceptibility at lower concentrations.
- This effect complicates resistance determination, particularly for emerging pathogens like Candida auris with undefined susceptibility breakpoints.
Purpose of the Study:
- To describe a protocol for differentiating echinocandin resistance from paradoxical growth in Candida auris isolates.
- To aid in accurate antifungal susceptibility testing for challenging fungal pathogens.
Main Methods:
- Development and description of a specific laboratory protocol.
- Application of the protocol to Candida auris isolates.
- Comparative analysis of growth patterns at varying echinocandin concentrations.
Main Results:
- The protocol effectively distinguishes between true echinocandin resistance and the paradoxical growth effect in Candida auris.
- Provides a clear method for classifying isolates that exhibit PGE.
Conclusions:
- Accurate identification of echinocandin resistance versus PGE is crucial for effective treatment of Candida auris infections.
- The described protocol offers a reliable solution for this diagnostic challenge in clinical settings.
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