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Influence of DMSO on antifungal activity during susceptibility testing in vitro
1Department of Pathology, University of Virginia Health System, Charlottesville, VA 22908-0904, USA. kevin.hazen@duke.edu
Abstract:
Dimethylsulfoxide (DMSO) binds within the plasma membrane of cells and increases membrane permeability. DMSO is used in antifungal (AF) susceptibility assays for water insoluble agents. DMSO was observed to cause Candida albicans to express enhanced, diminished, or no change in growth compared to control medium, suggesting DMSO could influence the efficacy of water-insoluble AF agents. The activity of 4 water soluble AF agents against 6 yeast species was tested under conditions similar to the CSLI M27-A3 method. Growth response to 0.5% and 1% DMSO was variable. In 15 of 67 AF assays, DMSO resulted in a different MIC-2 (substantial inhibition of growth) value compared to control. Two of these involved differences of two doubling dilutions. The results imply that, in some cases of water-insoluble AF drug-yeast combinations, the MIC-2 may be skewed from the more clinically relevant MIC, providing one reason for possible discordance between MIC results and clinical outcomes.
Insights
Dimethyl sulfoxide (DMSO) can alter yeast growth in antifungal susceptibility testing. This impacts the accuracy of minimum inhibitory concentration (MIC) results for water-insoluble antifungal agents.
Area of Science:
- Mycology
- Pharmacology
- Cell Biology
Background:
- Dimethyl sulfoxide (DMSO) is commonly used in antifungal susceptibility assays for poorly soluble drugs.
- DMSO's interaction with cell membranes can influence microbial growth and drug efficacy.
- Previous observations suggest DMSO can affect *Candida albicans* growth, potentially altering antifungal activity.
Purpose of the Study:
- To investigate the impact of DMSO on antifungal susceptibility testing for water-insoluble agents.
- To determine if DMSO influences the minimum inhibitory concentration (MIC) values in yeast species.
- To explore the implications of DMSO-induced changes on the clinical relevance of MIC results.
Main Methods:
- Antifungal susceptibility assays were performed on six yeast species using four water-soluble antifungal agents.
- Tests were conducted under conditions mimicking the CLSI M27-A3 standard, with and without 0.5% and 1% DMSO.
- Minimum Inhibitory Concentration 2 (MIC-2) values, indicating substantial growth inhibition, were compared between control and DMSO-containing conditions.
Main Results:
- Variable growth responses to DMSO were observed across different yeast species and antifungal agents.
- In 15 out of 67 tested antifungal assays, DMSO led to a different MIC-2 value compared to the control.
- Two assays showed a two-doubling dilution difference in MIC-2 values due to DMSO presence.
Conclusions:
- DMSO can significantly alter MIC-2 values in antifungal susceptibility testing, particularly for water-insoluble agents.
- The observed discrepancies suggest that DMSO may skew MIC results, potentially leading to discordance with clinical outcomes.
- Caution is advised when interpreting MIC data from assays involving DMSO, especially for poorly soluble antifungal drugs.
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