Clinical significance of azole antifungal drug cross-resistance in Candida glabrata

Anil A. Panackal, Jennifer L. Gribskov, Janet F. Staab, Katherine A. Kirby, Michael Rinaldi, Kieren Marr

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1740-1743
Number of pages4
JournalJournal of Clinical Microbiology
Volume44
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

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Fungal Drug Resistance
Candida glabrata
Azoles
Fluconazole
Itraconazole
Candidemia
Hematopoietic Stem Cells
Restriction Fragment Length Polymorphisms
Invasive Candidiasis
Pharmaceutical Preparations
Transplants
Infection
Voriconazole
Therapeutics

ASJC Scopus subject areas

  • Microbiology (medical)
  • Microbiology

Cite this

Clinical significance of azole antifungal drug cross-resistance in Candida glabrata. / Panackal, Anil A.; Gribskov, Jennifer L.; Staab, Janet F.; Kirby, Katherine A.; Rinaldi, Michael; Marr, Kieren.

In: Journal of Clinical Microbiology, Vol. 44, No. 5, 05.2006, p. 1740-1743.

Research output: Contribution to journalArticle

Panackal, Anil A. ; Gribskov, Jennifer L. ; Staab, Janet F. ; Kirby, Katherine A. ; Rinaldi, Michael ; Marr, Kieren. / Clinical significance of azole antifungal drug cross-resistance in Candida glabrata. In: Journal of Clinical Microbiology. 2006 ; Vol. 44, No. 5. pp. 1740-1743.
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