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. 2003 Jan;41(1):267-72.
doi: 10.1128/JCM.41.1.267-272.2003.

Characterization of heteroresistance to fluconazole among clinical isolates of Cryptococcus neoformans

T Yamazumi  1 , M A Pfaller, S A Messer, A K Houston, L Boyken, R J Hollis, I Furuta, R N Jones
Affiliations

Characterization of heteroresistance to fluconazole among clinical isolates of Cryptococcus neoformans

T Yamazumi et al. J Clin Microbiol. 2003 Jan.

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 microg/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 microg/ml, grew on agar with 64 microg 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 microg/ml. Subclones of three strains demonstrated a homogeneous population of resistant cells on medium containing 64 microg of fluconazole/ml. The resistance was sensitive to incubation temperature, that is, heteroresistance was demonstrable only at 30 degrees 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.

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Figures

FIG. 1.
FIG. 1.
Population analysis of the five isolates which were screened on fluconazole (FLCZ)-containing medium. Values on the y axis indicate the percentage of clonal populations which grew on the plate containing different concentrations of fluconazole (x axis).
FIG. 2.
FIG. 2.
Stability of fluconazole resistance after daily transfers in drug-free medium at 30°C. Shown are the MICs determined from E tests and the percentage of positive growth on medium containing 64 μg of fluconazole per ml for homogeneously resistant clones that were selected on medium with 64 μg of fluconazole per ml. •, 20.021.051-64; ▪, 20.067.025-64; ×, 20.067.061-64.
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References

    1. Armengou, A., C. Porcar, J. Mascaro, and F. Garcia-Bragado. 1996. Possible development of resistance to fluconazole during suppressive therapy for AIDS-associated cryptococcal meningitis. Clin. Infect. Dis. 23:1337-1338. - PubMed
    1. Barchiesi, F., R. J. Hollis, S. A. Messer, G. Scalise, M. G. Rinaldi, and M. A. Pfaller. 1995. Electrophoretic karyotype and in vitro antifungal susceptibility of Cryptococcus neoformans isolates from AIDS patients. Diagn. Microbiol. Infect. Dis. 23:99-103. - PubMed
    1. Barchiesi, F., D. Calabrese, D. Sanglard, L. Falconi Di Francesco, F. Caselli, D. Giannini, A. Giacometti, S. Gavaudan, and G. Scalise. 2000. Experimental induction of fluconazole resistance in Candida tropicalis ATCC 750. Antimicrob. Agents Chemother. 44:1578-1584. - PMC - PubMed
    1. Berg, J., C. J. Clancy, and M. H. Nguyen. 1998. The hidden danger of primary fluconazole prophylaxis for patients with AIDS. Clin. Infect. Dis. 26:186-187. - PubMed
    1. Brandt, M. E., M. A. Pfaller, R. A. Hajjeh, E. A. Graviss, J. Rees, E. D. Spitzer, R. W. Pinner, L. W. Mayer, et al. 1996. Molecular subtypes and antifungal susceptibilities of serial Cryptococcus neoformans isolates in human immunodeficiency virus associated cryptococcosis. J. Infect. Dis. 174:812-820. - PubMed

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