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Published on: October 21, 2010
Standardization of antifungal susceptibility testing
1Department of Pathology, University of Iowa College of Medicine, Iowa City 52242-1009, USA.
Abstract:
The application of in-vitro antifungal susceptibility testing to clinical research and to the guidance of antifungal therapy has been limited by a lack of reproducibility and uncertain clinical relevance. As a result of studies of the identified variables impacting on in-vitro susceptibility results, the National Committee for Clinical Laboratory Standards have proposed a standardized antifungal susceptibility test method M27-P. The degree of intra- and inter-laboratory reproducibility which can be achieved with this method have been defined in multi-laboratory collaborative studies. More convenient methods (microdilution broth and stable gradient technology) have been evaluated relative to the proposed standard method and the potential for a similar process with a disc diffusion method is apparent. A modification of this standard method for susceptibility testing of filamentous fungi appears promising. The existence of a standardized method and of alternative methods with a defined relationship to the proposed standard, facilitates meaningful analysis of published studies addressing the issue of clinical relevance of antifungal susceptibility testing. As a result of this process, correlation of MICs determined in vitro with clinical response to therapy is beginning to emerge, most notably in relation to fluconazole therapy for oropharyngeal candidosis associated with infection with the human immunodeficiency virus.
Insights
Standardized antifungal susceptibility testing methods improve reproducibility and clinical relevance. This allows for better analysis of in vitro results, aiding antifungal therapy guidance, particularly for HIV-associated candidosis.
Area of Science:
- Medical Microbiology
- Clinical Mycology
- Pharmacology
Background:
- In vitro antifungal susceptibility testing (AFST) has faced challenges in reproducibility and clinical relevance.
- Limited standardization has hindered the reliable application of AFST in clinical research and therapy guidance.
Purpose of the Study:
- To address the limitations of AFST by developing and evaluating standardized methods.
- To establish reproducible and clinically relevant in vitro testing protocols for antifungal agents.
Main Methods:
- Development and validation of a standardized method (M27-P) by the National Committee for Clinical Laboratory Standards.
- Evaluation of alternative methods like microdilution broth and stable gradient technology against the standard.
- Assessment of a disc diffusion method and modification for filamentous fungi.
Main Results:
- Multi-laboratory studies confirmed the intra- and inter-laboratory reproducibility of the proposed standard method.
- Alternative methods demonstrated a defined relationship to the standard, offering convenience.
- A modified standard method for filamentous fungi showed promise.
Conclusions:
- The availability of standardized and validated alternative AFST methods facilitates meaningful analysis of clinical relevance.
- Emerging correlations between in vitro minimum inhibitory concentrations (MICs) and clinical outcomes are evident.
- This progress is particularly notable for fluconazole in treating HIV-associated oropharyngeal candidosis.
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