895. Influence of Dimethyl Sulfoxide on Antifungal Minimal Inhibitory Concentrations
Session: Poster Abstract Session: Antifungal Therapy
Saturday, October 22, 2011
Room: Poster Hall B1
Handouts
  • 895_KevinHazen.pdf (6.7 MB)
  • Background: One percent (v/v) DMSO is included in the test medium used to assay inhibitory activity of water insoluble antifungal agents by the CLSI M27-A3 standard susceptibility method. How DMSO influences yeast cell growth and the minimal inhibitory concentration outcome in the CLSI test format is not well established. Methods: CLSI M27-A3 microbroth dilution assay conditions were used to test two or three strains of each of six Candida species, C. albicans (CA), C. dubliniensis (CD), C. glabrata (CG), C. orthopsilosis (CO), C. parapsilosis (CP) and C. tropicalis (CT) for their response against a range of DMSO concentrations (04%) and for their growth response to a dilution series of the water soluble drugs micafungin (MFN), fluconazole (FCZ), 5-flucytosine (5FC), and nikkomycin Z (NKZ) in the presence or absence of 1 % DMSO. Cell buttons were scored visually and cell turbidity was assessed spectrophotometrically. The MIC-0 and MIC-2 were determined when cells were tested against antifungal drugs. Results: Enhanced cell density was seen with 2% DMSO for two strains, one of CA and one of CO. All isolates displayed decreased growth when exposed to 4% DMSO. Growth of CA and CG strains was unaffected at 1% DMSO in the DMSO titer assay, while growth of CT and CD strains was diminished. Strains of CP and CO varied in their response to 1% DMSO. Curiously, when exposed to 1% DMSO during the drug assays all strains exhibited instances of enhanced growth. Only two strains, one of CA and one of CP expressed enhanced growth consistently. Of the 86 drug-bug combinations tested to date four resulted in MIC-2 changes that were two doubling dilutions different (3 of 4 resulted in lower MIC-2 values). Thirty-five (ca. 40%) changes in MIC-0 and MIC-2 values occurred as a result of exposure to 1% DMSO. Twenty (57%) were changes in MIC-2 values (the CLSI recommended MIC to report for all four drugs). Conclusion: The results suggest that water insoluble antifungal agents tested in the presence of DMSO may exhibit inhibitory or stimulatory activity not directly related to the drug on some yeasts. If so, adjustments to how the MIC for the water insoluble drugs is reported may need to be addressed.

    Subject Category: M. Mycology including clinical and basic studies of fungal infections

    Kevin Hazen, PhD and Stephen Cook, M.D., University of Virginia, Charlottesville, VA

    Disclosures:

    K. Hazen, None

    S. Cook, None

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