Multiple Patterns of Gene Expression with Fluconazole Resistance in a Patient with Candida glabrata Oropharyngeal Candidiasis.

S.W. REDDING, S.P. SAVILLE, W.S. WHITE, B.J. COCO, W.R. KIRKPATRICK, A.W. FOTHERGILL, M.G. RINALDI, T.F. PATTERSON, J.L. LOPEZ-RIBOT

Abstract: 

Background: Our group has reported previously on a patient receiving radiation for head and neck cancer who demonstrated increased resistance to fluconazole (FLU) of two distinct strains after treatment for Candida glabrata oropharyngeal candidiasis (OPC). The purpose of this study was to assess gene expression in representative isolates of the C. glabrata genes CDR1, CDR2, and ERG11 implicated in azole resistance. Methods: Weekly oral swab and swish samples for yeasts were obtained from a patient receiving radiation for head and neck cancer. Positive cultures were identified using standard microbiological and biochemical procedures. Isolates were subcultured for characterization using DNA typing techniques and macrobroth antifungal susceptibility testing according to NCCLS standards. Expression of the C. glabrata genes encoding lanosterol demethylase (ERG11) and efflux pumps (CDR1 and CDR2) was monitored in matched sets of susceptible and resistant isolates by Northern blot. Results: Two distinct strains of C. glabrata (A and B) were identified and tested over four visits beginning with FLU therapy. Strain A showed a rapid increase in FLU MIC from 8.0 to >64µg/ml over two weeks. One month after FLU was discontinued FLU MIC remained at >64µg/ml. Expression of CDR1, CDR2, and ERG 11 remained stable over this period. The FLU MIC of Strain B remained stable at 8.0 µg/ml over the two weeks of drug therapy. However, one month after FLU was discontinued, MIC increased to >64 µg/ml. Levels of CDR1, CDR2, and ERG11 expression were constant over the two weeks of FLU therapy but were significantly elevated in an isolate obtained at the one month follow-up consistent with the acute rise of FLU MIC. Conclusion: Gene expression associated with the development of FLU resistance in C. glabrata is highly variable among multiple strains in the same patient.
2002

abstract No: 

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Full conference title: 

42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 42nd