Fluconazole tolerance in clinical isolates of Cryptococcus neoformans
Author(s) -
Venkateswarlu Kanamarlapudi,
Maureen B. Taylor,
N. J. Manning,
Michael G. Rinaldi,
Steven L. Kelly
Publication year - 1997
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.41.4.748
Subject(s) - fluconazole , cryptococcus neoformans , microbiology and biotechnology , ergosterol , biology , amphotericin b , fungi imperfecti , sterol , mycosis , drug resistance , cryptococcus , antifungal , immunology , biochemistry , cholesterol
Eleven isolates of Cryptococcus neoformans were investigated to determine the biochemical basis of their tolerance to fluconazole. The MICs of fluconazole for three isolates with low-level resistance were 3- to 6-fold higher than those for sensitive isolates, while the MICs for four isolates with high-level resistance were 100- to 200-fold higher than those for sensitive isolates. The level of ergosterol present in the isolates varied, and those which had relatively low levels of ergosterol were resistant to amphotericin B. Changes in the affinity of the target enzyme (sterol 14alpha-demethylase) and decreases in the cellular content of fluconazole seemed to be responsible for the resistance in isolates with low-level and high-level resistance, respectively.
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