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Toward the consensus of definitions for the phenomena of antifungal tolerance and persistence in filamentous fungi

Summary

Scientists have proposed clear definitions and testing methods for two drug-resistance phenomena in fungi that cause infections. Unlike typical drug resistance, tolerance and persistence allow fungi to survive antifungal medications but in different ways: tolerance affects most spores while persistence affects only a small fraction. By standardizing how these phenomena are tested using fungal spores and measuring how quickly drugs kill them, researchers can better understand treatment failures and develop better therapies.

Background

Antifungal drug tolerance and persistence are increasingly recognized in fungal pathogens but lack standardized definitions and methodologies, particularly for filamentous fungi. These phenomena are distinct from antimicrobial resistance and are clinically relevant as they allow microorganisms to survive supra-MIC drug concentrations. In bacteria, these terms have been well-defined for over two decades, but fungal research lacks consensus terminology.

Objective

To propose tailored definitions for tolerance and persistence in filamentous fungi and suggest standardized laboratory methods to detect and investigate these phenomena. The authors aim to ensure consistency in literature and facilitate understanding across the field.

Results

The paper presents tailored definitions where tolerance is defined as survival of all or high proportion of spores at supra-MIC concentrations with extended MDK values, while persistence involves survival of a small fraction (<0.1%) of spores with normal initial killing but delayed final elimination. A drug killing ≥90% of spores within 24 hours is considered fungicidal for applicability of these definitions.

Conclusion

Standardized definitions and methodologies for tolerance and persistence in filamentous fungi are essential for consistency and comparability in research. The proposed guidelines using conidia and time-kill assays harmonize with resistance detection methods and provide practical frameworks for future antifungal research.
  • Published in:mBio,
  • Study Type:Perspective Article,
  • Source: PMID: 39998174, DOI: 10.1128/mbio.03475-24
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