Fluconazole Susceptibility of Vaginal Isolates Obtained from Women with Complicated Candida Vaginitis: Clinical Implications

Author:

Sobel J. D.1,Zervos M.2,Reed B. D.3,Hooton T.4,Soper D.5,Nyirjesy P.6,Heine M. W.7,Willems J.8,Panzer H.9

Affiliation:

1. Department of Internal Medicine, Wayne State University, Detroit, Michigan

2. Department of Internal Medicine, William Beaumont Hospital, Royal Oak, Mich.

3. Department of Family Medicine, University of Michigan, Ann Arbor, Michigan

4. Department of Internal Medicine, University of Washington, Seattle, Washington

5. Department of Obstetrics and Gynecology, Medical College of South Carolina, Charleston, South Carolina

6. Department of Obstetrics and Gynecology, Jefferson Medical College, Philadelphia, Pennsylvania

7. Department of Obstetrics and Gynecology, University of Arizona, Tucson, Arizona

8. Scripps Clinic, La Jolla, California

9. Pfizer Pharmaceutical Trials TAC, New York, New York

Abstract

ABSTRACT Despite considerable evidence of azole resistance in oral candidiasis due to Candida species, little is known about the azole susceptibilities of the genital tract isolates responsible for vaginitis. The fluconazole susceptibilities of vaginal isolates obtained during a multicenter study of 556 women with complicated Candida vaginitis were determined by evaluating two fluconazole treatment regimens. Of 393 baseline isolates of Candida albicans , 377 (96%) were highly susceptible to fluconazole (MICs, <8 μg/ml) and 14 (3.6%) were resistant (MICs, ≥64 μg/ml). Following fluconazole therapy, one case of in vitro resistance developed during 6 weeks of monitoring. In accordance with the NCCLS definition, in vitro fluconazole resistance correlated poorly with the clinical response, although a trend of a higher mycological failure rate was found (41 versus 19.6% on day 14). By using an alternative breakpoint of 1 μg/ml, based upon the concentrations of fluconazole achievable in vaginal tissue, no significant differences in the clinical and mycological responses were observed when isolates ( n = 250) for which MICs were ≤1 μg/ml were compared with isolates ( n = 30) for which MICs were >1 μg/ml, although a trend toward an improved clinical outcome was noted on day 14 (odds ratio, >2.7; 95% confidence interval, 0.91, 8.30). Although clinical failure was uncommon, symptomatic recurrence or mycological relapse almost invariably occurred with highly sensitive strains (MICs, <1.0 μg/ml). In vitro fluconazole resistance developed in 2 of 18 initially susceptible C. glabrata isolates following fluconazole exposure. Susceptibility testing for women with complicated Candida vaginitis appears to be unjustified.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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