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Journal of Clinical Microbiology, February 2008, p. 551-559, Vol. 46, No. 2
0095-1137/08/$08.00+0     doi:10.1128/JCM.01952-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Selection of a Surrogate Agent (Fluconazole or Voriconazole) for Initial Susceptibility Testing of Posaconazole against Candida spp.: Results from a Global Antifungal Surveillance Program{triangledown}

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

Departments of Pathology,1 Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa2

Received 3 October 2007/ Returned for modification 27 November 2007/ Accepted 11 December 2007

There are currently no FDA-approved broth microdilution antifungal susceptibility testing products or interpretive breakpoints for susceptibility testing of the new triazole posaconazole. Fluconazole and voriconazole are in the same triazole class as posaconazole, have CLSI-approved interpretive MIC breakpoints, and are available on some commercially available MIC panels. We investigated whether one or both of these agents may be useful as a surrogate marker for posaconazole susceptibility. Fluconazole, voriconazole, and posaconazole MIC results for 10,807 isolates of Candida spp. were analyzed to validate a potential surrogate marker for posaconazole activity against indicated species. For illustrative purposes, we applied the voriconazole MIC breakpoints to posaconazole (susceptible, ≤1 µg/ml; susceptible dose dependent, 2 µg/ml; resistant, ≥4 µg/ml) and compared these MIC results and categorical interpretations with those of fluconazole and voriconazole by using regression statistics and categorical agreement. For all 10,807 isolates, the absolute categorical agreement was 91.1% (0.1% very major errors [VME], 1.2% major errors [ME], and 7.6% minor errors [M]) using fluconazole as the surrogate marker and 97.7% (0.3% VME 0.1% ME, and 1.9% M) using voriconazole as the surrogate. The results with fluconazole improved to a categorical agreement of 93.7% (0.1% VME, 0.2% ME, and 6.0% M) when results for Candida krusei (not indicated for fluconazole testing) were omitted. Either fluconazole or voriconazole MIC results may serve as surrogate markers to predict the susceptibility of Candida spp. to posaconazole.

* Corresponding author. Mailing address: Medical Microbiology Division, C606 GH, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242. Phone: (319) 356-8615. Fax: (319) 356-4916. E-mail: michael-pfaller{at}uiowa.edu

{triangledown} Published ahead of print on 19 December 2007.

Journal of Clinical Microbiology, February 2008, p. 551-559, Vol. 46, No. 2
0095-1137/08/$08.00+0     doi:10.1128/JCM.01952-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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