Journal article
Characterization of Heteroresistance to Fluconazole among Clinical Isolates of Cryptococcus neoformans
Journal of clinical microbiology, Vol.41(1), pp.267-272
01/2003
DOI: 10.1128/JCM.41.1.267-272.2003
PMCID: PMC149577
PMID: 12517859
Abstract
Strains of
Cryptococcus neoformans
expressing heteroresistance to fluconazole have been described previously. The present study was conducted to investigate the prevalence of heteroresistance among clinical isolates of
C. neoformans
and to characterize the heteroresistant phenotypes. A total of 107 clinical isolates of
C. neoformans
for which the MICs of fluconazole ranged from 0.25 to 32 μg/ml were selected. The isolates were chosen to represent a broad geographic distribution. Of the 107
C. neoformans
isolates tested, 4 grew on medium containing fluconazole at concentrations that were four to eight times higher than the MICs for each strain. A fifth isolate, for which the fluconazole MIC was 32 μg/ml, grew on agar with 64 μg of fluconazole per ml. These five isolates (4.7% of the total number) were confirmed to exhibit heteroresistant compositions by population analysis. The degree and frequency of resistance varied among the isolates. Stepwise selection by exposure to fluconazole resulted in subclones of all five strains for which the fluconazole MIC was >64 μg/ml. Subclones of three strains demonstrated a homogenous population of resistant cells on medium containing 64 μg of fluconazole/ml. The resistance was sensitive to incubation temperature, that is, heteroresistance was demonstrable only at 30°C by agar-based tests, and was reversible through serial transfers on fluconazole-free medium over a period of 8 days. These results suggest that the fluconazole-heteroresistant phenotype of
C. neoformans
exists in a significant proportion of clinical isolates and that fluconazole resistance can be developed by selection from heteroresistant clones and induction by exposure to fluconazole.
Details
- Title: Subtitle
- Characterization of Heteroresistance to Fluconazole among Clinical Isolates of Cryptococcus neoformans
- Creators
- T Yamazumi - University of IowaM. A Pfaller - University of IowaS. A Messer - University of IowaA. K Houston - University of IowaL Boyken - University of IowaR. J Hollis - University of IowaI Furuta - Kindai UniversityR. N Jones - Tufts University
- Resource Type
- Journal article
- Publication Details
- Journal of clinical microbiology, Vol.41(1), pp.267-272
- DOI
- 10.1128/JCM.41.1.267-272.2003
- PMID
- 12517859
- PMCID
- PMC149577
- NLM abbreviation
- J Clin Microbiol
- ISSN
- 0095-1137
- eISSN
- 1098-660X
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 01/2003
- Academic Unit
- Epidemiology; Pathology
- Record Identifier
- 9984184003102771
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