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Susceptibility testing of fungi--current status and open questions
Michael Seibold1, Kathrin Tintelnot
1Robert Koch-Institut, Mykologie, Nordufer 20, 13353 Berlin, Germany.
Abstract:
The increase of fungal infections and the improvement of therapeutical options demand reliable antifungal susceptibility testing. In vitro susceptibility testing of fungi--in contrast to bacteria--is not yet established as a routine method. The NCCIS (National Committee for Clinical Laboratory Standards) guidelines for susceptibility testing of yeasts (and proposed for hyphomycetes) are most important for standardization. Meanwhile, essential parts of this test procedure are accepted, but it should still be improved. The concept of using only one test medium for all drugs and test organisms is not realized so far. There are also some test situations that prevent the NCCLS standard from being applied. Based on our experience, this article describes the NCCLS methods and their modifications. It places emphasis on lipophilic drugs showing controversies despite standardization. Furthermore, the prediction of MICs on the clinical outcome is discussed. Since there are some pitfalls in testing antifungals, this should be done in experienced laboratories only. The MIC has to be regarded as only one, but an important, factor in the management of fungal diseases. Host-, drug-, and pathogen-specific data should be considered simultaneously.
Insights
Reliable antifungal susceptibility testing is crucial due to rising fungal infections. Current methods, like National Committee for Clinical Laboratory Standards (NCCLS) guidelines, require further refinement for routine use.
Area of Science:
- Medical Mycology
- Clinical Microbiology
- Pharmacology
Background:
- Rising incidence of fungal infections necessitates accurate antifungal susceptibility testing (AST).
- AST for fungi is not yet a routine clinical laboratory method, unlike bacterial AST.
- Standardization efforts are ongoing, with National Committee for Clinical Laboratory Standards (NCCLS) guidelines being pivotal for yeasts and proposed for hyphomycetes.
Purpose of the Study:
- To describe and discuss modifications of NCCLS antifungal susceptibility testing methods based on practical experience.
- To highlight challenges and controversies in antifungal susceptibility testing, particularly for lipophilic drugs.
- To explore the correlation between Minimum Inhibitory Concentrations (MICs) and clinical outcomes.
Main Methods:
- Review and modification of established NCCLS guidelines for in vitro antifungal susceptibility testing.
- Focus on specific challenges related to lipophilic antifungal agents.
- Analysis of factors influencing the prediction of clinical outcomes from MIC values.
Main Results:
- Essential components of NCCLS guidelines are accepted but require further improvement and standardization.
- A universal test medium for all antifungal drugs and organisms is not yet realized.
- Specific testing scenarios pose challenges to the application of current NCCLS standards, especially for lipophilic drugs.
Conclusions:
- Antifungal susceptibility testing should be performed in experienced laboratories due to inherent complexities and potential pitfalls.
- The Minimum Inhibitory Concentration (MIC) is a critical but not sole determinant in managing fungal infections.
- A comprehensive management approach requires simultaneous consideration of host, drug, and pathogen-specific data.