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Antimicrobial Agents and Chemotherapy, July 1999, p. 1621-1630, Vol. 43, No. 7
Departments of
Medicine1 and
Pathology,
Received 8 February 1999/Returned for modification 29 March
1999/Accepted 7 May 1999
Mechanisms of resistance to azoles in Candida albicans,
the main etiologic agent of oropharyngeal candidiasis (OPC), include alterations in the target enzyme (lanosterol demethylase) and increased
efflux of drug. Previous studies on mechanisms of resistance have been
limited by the fact that only a single isolate from each OPC episode
was available for study. Multiple isolates from each OPC episode were
evaluated with oral samples plated in CHROMagar Candida with and
without fluconazole to maximize detection of resistant yeasts. A total
of 101 isolates from each of three serial episodes of OPC from four
different patients were evaluated. Decreasing geometric means of
fluconazole MICs with serial episodes of infection were detected in the
four patients. However, 8-fold or larger (up to 32-fold) differences in
fluconazole MICs were detected within isolates recovered at the same
time point in 7 of 12 episodes. Strain identity was analyzed by DNA
typing techniques and indicated that isolates from each patient
represented mainly isogenic strains, but differed among patients. A
Northern blot technique was used to monitor expression of
ERG11 (encoding lanosterol demethylase) and genes coding
for efflux pumps. This analysis revealed that clinical isolates
obtained from the same patient and episode were phenotypically
heterogeneous in their patterns of expression of these genes involved
in fluconazole resistance. These results demonstrate the complexity of
the distribution of the molecular mechanisms of antifungal drug
resistance and indicate that different subpopulations of yeasts may
coexist at a given time in the same patient and may develop resistance
through different mechanisms.
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Multiple Resistant Phenotypes of Candida albicans
Coexist during Episodes of Oropharyngeal Candidiasis in Human
Immunodeficiency Virus-Infected Patients
*
Corresponding author. Mailing address: Department of
Medicine, Division of Infectious Diseases, The University of Texas
Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78284-7881. Phone: (210) 567-1981. Fax: (210) 567-3303. E-mail: ribot{at}uthscsa.edu.
Antimicrobial Agents and Chemotherapy, July 1999, p. 1621-1630, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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