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Journal of Clinical Microbiology, May 2006, p. 1740-1743, Vol. 44, No. 5
0095-1137/06/$08.00+0     doi:10.1128/JCM.44.5.1740-1743.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Clinical Significance of Azole Antifungal Drug Cross-Resistance in Candida glabrata

Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington,¹ Departments of Medicine,² Microbiology, University of Washington, Seattle, Washington,⁴ Fungus Testing Laboratory, University of Texas, San Antonio, Texas³

Received 3 February 2006/ Returned for modification 22 February 2006/ Accepted 27 February 2006

Candida glabrata, which can become resistant to fluconazole, is a common cause of bloodstream infection. This study was performed to determine the significance of cross-resistance to new azole drugs among C. glabrata isolates recovered as a cause of infection in azole-treated hematopoietic stem cell transplant (HSCT) recipients. Seven cases of invasive candidiasis caused by C. glabrata occurred in HSCT recipients who were receiving azole therapy between January 2000 and December 2004 in our institution. Case characteristics were ascertained. Sequential colonizing and invasive isolates were examined to determine susceptibilities to fluconazole, itraconazole, and voriconazole, and molecular relatedness by restriction fragment length polymorphism (RFLP) analysis. Twenty-three C. glabrata isolates were recovered from 4 patients who developed candidemia while receiving fluconazole and three patients who developed candidemia while receiving voriconazole. The mode MICs of fluconazole, itraconazole, and voriconazole for these isolates were 64 µg/ml (range, 4 to 64 µg/ml), 2 µg/ml (range, 0.25 to 16 µg/ml), and 1 µg/ml (range, 0.03 to 16 µg/ml), respectively. Kendall tau b correlation coefficients demonstrated significant associations between the MICs of voriconazole with fluconazole (P = 0.005) and itraconazole (P = 0.008). Colonizing and invasive isolates exhibiting variable susceptibilities had similar RFLP patterns. These observations suggest that C. glabrata exhibits considerable clinically significant cross-resistance between older azole drugs (fluconazole and itraconazole) and voriconazole. Caution is advised when considering voriconazole therapy for C. glabrata candidemia that occurs in patients with extensive prior azole drug exposure.

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