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Antimicrobial Agents and Chemotherapy, January 2004, p. 161-167, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.161-167.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Fungicidal Activity of Fluconazole against Candida albicans in a Synthetic Vagina-Simulative Medium

Mahomed-Yunus S. Moosa,1,2 Jack D. Sobel,1 Hussain Elhalis,3 Wenjin Du,3 and Robert A. Akins3*

Division of Infectious Diseases, Department of Internal Medicine,1 Department of Immunology and Microbiology,2 Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan 482013

Received 16 April 2003/ Returned for modification 29 July 2003/ Accepted 7 October 2003

Fluconazole (FLZ) has emerged as a highly successful agent in the management of systemic infections of Candida. Cure rates for symptomatic candidiasis following single 150-mg FLZ dose therapy exceed 90%. In vitro, however, FLZ is fungistatic only in a narrow pH range and is not effective at vaginal pH, 4.2. This study evaluated the effect of FLZ on Candida albicans under in vitro conditions resembling the vaginal microenvironment, using vagina-simulative medium (VS). We found that FLZ was fungicidal for C. albicans in VS, but not in other media at the same pH, 4.2. In VS, FLZ was fungicidal at concentrations of >=8 µg/ml and reduced viability by greater than 99.9%. Analysis of the components of VS indicated that 17 mM acetic acid, a concentration achieved in the vagina, was responsible for the synergistic, fungicidal effect. This effect was not seen at neutral pH. Other substrates were not effective substitutes for acetic acid; however, short-chained carboxylic acids, glyoxylate and malonate, were effective. Most strains of C. albicans that were resistant to FLZ under standard conditions were killed by FLZ plus acetate. Other species of Candida were also killed, except C. krusei and C. glabrata. This study shows that FLZ has fungicidal activity for Candida species under in vitro conditions that mimic the vaginal microenvironment. This raises the possibility that FLZ may also have fungicidal effects during treatment of vaginal candidiasis. Elucidating the mechanism by which FLZ and acetate interact may disclose vulnerable pathways that could be exploited in drug development.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine Detroit, MI 48201. Phone: (313) 577-0419. Fax: (313) 577-0419. E-mail: rakins{at}med.wayne.edu.

Antimicrobial Agents and Chemotherapy, January 2004, p. 161-167, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.161-167.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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