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Journal of Clinical Microbiology, February 2006, p. 529-535, Vol. 44, No. 2
0095-1137/06/$08.00+0     doi:10.1128/JCM.44.2.529-535.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Triazole Cross-Resistance among Candida spp.: Case Report, Occurrence among Bloodstream Isolates, and Implications for Antifungal Therapy

Shelley S. Magill,1,2* Christine Shields,2 Cynthia L. Sears,1 Michael Choti,3 and William G. Merz2

Infectious Diseases Division, Department of Medicine,1 Microbiology Division, Department of Pathology,2 Department of Surgery, Johns Hopkins University School of Medicine and Johns Hopkins Hospital, Baltimore, Maryland3

Received 12 August 2005/ Returned for modification 14 October 2005/ Accepted 16 November 2005

Candida spp. are common causes of bloodstream infections among hospitalized patients. Fluconazole (FLC) remains a first-line therapy for candidemia; and voriconazole (VRC), an expanded-spectrum triazole, was recently approved for the treatment of candidemia in nonneutropenic patients. In vitro studies have suggested that VRC has potent activity against Candida spp. with reduced susceptibilities to FLC. We present a case report of invasive candidiasis and candidemia due to a Candida glabrata isolate that developed resistance to all currently available triazole antifungals after a course of FLC treatment. This case prompted us to determine the frequency of cross-resistance among bloodstream Candida isolates collected during a recent 12-month period at a large, academic medical center. FLC MICs were determined for 125 of 153 isolates (81.7%). Thirty of 125 isolates (24%) were resistant or showed reduced susceptibilites to FLC (MICs ≥ 16 µg/ml). When 28 of these 30 isolates were tested for their VRC susceptibilities, 9 (32%) had MICs that were ≥2 µg/ml. Five of these nine isolates were C. glabrata, two isolates were Candida tropicalis, one isolate was Candida albicans, and one isolate was Candida parapsilosis. All five Candida krusei isolates tested had VRC MICs ≤0.5 µg/ml. These data have prompted the introduction of reflexive FLC susceptibility testing of first bloodstream Candida isolates at our institution. The case report and our data also suggest that VRC should be avoided as initial therapy in unstable patients with invasive candidiasis, particularly in the setting of prior azole exposure. Studies are needed to define the clinical significance of in vitro resistance to the newer antifungal agents.

* Corresponding author. Mailing address: Infectious Diseases Division, Johns Hopkins University School of Medicine, 1830 E. Monument St., 4th Floor, Baltimore, MD 21205. Phone: (410) 614-9690. Fax: (410) 955-7889. E-mail: smagill2{at}jhmi.edu.

Journal of Clinical Microbiology, February 2006, p. 529-535, Vol. 44, No. 2
0095-1137/06/$08.00+0     doi:10.1128/JCM.44.2.529-535.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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