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Published on: February 14, 2018
Can We Improve Antifungal Susceptibility Testing?
Charlotte Durand1, Danièle Maubon1,2, Muriel Cornet1,2
1TIMC, Univ Grenoble Alpes, CNRS, Grenoble INP, Grenoble, France.
Abstract:
Systemic antifungal agents are increasingly used for prevention or treatment of invasive fungal infections, whose prognosis remains poor. At the same time, emergence of resistant or even multi-resistant strains is of concern as the antifungal arsenal is limited. Antifungal susceptibility testing (AFST) is therefore of key importance for patient management and antifungal stewardship. Current AFST methods, including reference and commercial types, are based on growth inhibition in the presence of an antifungal, in liquid or solid media. They usually enable Minimal Inhibitory Concentrations (MIC) to be determined with direct clinical application. However, they are limited by a high turnaround time (TAT). Several innovative methods are currently under development to improve AFST. Techniques based on MALDI-TOF are promising with short TAT, but still need extensive clinical validation. Flow cytometry and computed imaging techniques detecting cellular responses to antifungal stress other than growth inhibition are also of interest. Finally, molecular detection of mutations associated with antifungal resistance is an intriguing alternative to standard AFST, already used in routine microbiology labs for detection of azole resistance in Aspergillus and even directly from samples. It is still restricted to known mutations. The development of Next Generation Sequencing (NGS) and whole-genome approaches may overcome this limitation in the near future. While promising approaches are under development, they are not perfect and the ideal AFST technique (user-friendly, reproducible, low-cost, fast and accurate) still needs to be set up routinely in clinical laboratories.
Insights
Antifungal susceptibility testing (AFST) is crucial for invasive fungal infections due to rising resistance. New methods aim to reduce the long turnaround time of current growth-based assays.
Area of Science:
- Medical Mycology
- Clinical Microbiology
- Antimicrobial Resistance
Background:
- Invasive fungal infections (IFIs) have a poor prognosis, necessitating effective systemic antifungal agents.
- The emergence of antifungal-resistant strains poses a significant threat due to a limited antifungal drug arsenal.
- Antifungal susceptibility testing (AFST) is vital for guiding patient treatment and promoting antifungal stewardship.
Purpose of the Study:
- To review current Antifungal Susceptibility Testing (AFST) methods for invasive fungal infections.
- To highlight the limitations of existing AFST, primarily their long turnaround times (TAT).
- To explore innovative AFST techniques under development for improved clinical application.
Main Methods:
- Review of current reference and commercial AFST methods based on growth inhibition (MIC determination).
- Exploration of novel AFST approaches including MALDI-TOF, flow cytometry, and computed imaging.
- Discussion of molecular methods for detecting resistance mutations and future whole-genome sequencing (WGS) applications.
Main Results:
- Current AFST methods, while clinically applicable for MIC determination, suffer from lengthy turnaround times.
- Emerging techniques like MALDI-TOF offer faster results but require further clinical validation.
- Molecular methods and WGS show promise for rapid detection of resistance, though limitations remain.
Conclusions:
- The development of rapid and accurate AFST is critical for managing invasive fungal infections and combating resistance.
- Innovative techniques show promise but require further validation to become routine clinical tools.
- The ideal AFST method, balancing speed, accuracy, cost, and usability, is yet to be established for widespread clinical adoption.
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