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Journal of Clinical Microbiology, January 2007, p. 70-75, Vol. 45, No. 1
0095-1137/07/$08.00+0     doi:10.1128/JCM.01551-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Use of Fluconazole as a Surrogate Marker To Predict Susceptibility and Resistance to Voriconazole among 13,338 Clinical Isolates of Candida spp. Tested by Clinical and Laboratory Standards Institute-Recommended Broth Microdilution Methods{triangledown}

M. A. Pfaller,1,2* S. A. Messer,1 L. Boyken,1 C. Rice,1 S. Tendolkar,1 R. J. Hollis,1 and D. J. Diekema1,3

Departments of Pathology,1 Medicine, Roy J. and Lucille A. Carver College of Medicine,3 Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa 522422

Received 26 July 2006/ Returned for modification 10 October 2006/ Accepted 16 October 2006

Clinical laboratories frequently face the problem of delayed availability of commercially prepared approved reagents for performing susceptibility testing of new antimicrobials. Although this problem is encountered more often with antibacterial agents, it is also an issue with antifungal agents. A current example is voriconazole, a new triazole antifungal with an expanded spectrum and potency against Candida spp., Aspergillus spp., and other opportunistic fungal pathogens. The present study addresses the use of fluconazole as a surrogate marker to predict the susceptibility of Candida spp. to voriconazole. Reference broth microdilution MIC results for 13,338 strains of Candida spp. isolated from more than 200 medical centers worldwide were used. Voriconazole MICs and interpretive categories (susceptible, ≤1 µg/ml; susceptible dose dependent, 2 µg/ml; resistant, ≥4 µg/ml) were compared with those of fluconazole by regression statistics and error rate bounding analyses. For all 13,338 isolates, the absolute categorical agreement was 91.6% (false susceptible or very major error [VME], 0.0%). Since voriconazole is 16- to 32-fold more potent than fluconazole, the performance of fluconazole as a surrogate marker for voriconazole susceptibility was improved by designating those isolates with fluconazole MICs of ≤32 µg/ml as being susceptible to voriconazole, resulting in a categorical agreement of 97% with 0.1% VME. Clinical laboratories performing antifungal susceptibility testing of fluconazole against Candida spp. can reliably use these results as surrogate markers until commercial FDA-approved voriconazole susceptibility tests become available.

* Corresponding author. Mailing address: Medical Microbiology Division, C606 GH, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242. Phone: (319) 384-9566. Fax: (319) 356-4916. E-mail: michael-pfaller{at}uiowa.edu.

{triangledown} Published ahead of print on 1 November 2006.

Journal of Clinical Microbiology, January 2007, p. 70-75, Vol. 45, No. 1
0095-1137/07/$08.00+0     doi:10.1128/JCM.01551-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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