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Antimicrobial Agents and Chemotherapy, January 2007, p. 35-39, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00474-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Association of Fluconazole Area under the Concentration-Time Curve/MIC and Dose/MIC Ratios with Mortality in Nonneutropenic Patients with Candidemia{triangledown}

Manjunath P. Pai,1 Robin S. Turpin,2,3 and Kevin W. Garey4*

University of New Mexico, Albuquerque, New Mexico,1 Merck & Co., West Point, Pennsylvania,2 Jefferson Medical College, Philadelphia, Pennsylvania,3 University of Houston, Houston, Texas4

Received 18 April 2006/ Returned for modification 21 July 2006/ Accepted 29 October 2006

The present study tested in vitro susceptibility of Candida bloodstream isolates to fluconazole to determine if the ratio of the fluconazole area under the concentration-time curve (AUC) or weight-normalized daily dose (dosewn) to MIC correlated with mortality. Fluconazole susceptibility and outcome data were determined for 77 patients with a positive Candida blood culture between 2002 and 2005. The most commonly isolated Candida species were C. albicans (64%), C. glabrata (14%), C. parapsilosis (8%), C. tropicalis (6%), and C. lusitaniae (4%). Only two isolates were classified as fluconazole resistant by the CLSI M27-A2 method. Fluconazole MICs were highest against C. glabrata relative to other Candida species. Overall the crude mortality assessed at hospital discharge was 19.4% (n = 15). Mortality rates by species were as follows: C. albicans, 16.3%; C. glabrata, 36.4%; C. parapsilosis, 0%; C. tropicalis, 0%; C. lusitaniae, 33.3%. A mortality rate of 50% was noted among patients infected with nonsusceptible isolates (MIC ≥ 16 µg/ml) compared to 18% for patients infected with susceptible (MIC ≤ 8 µg/ml) isolates (P = 0.17). The fluconazole dosewn/MIC (24-h) values were significantly higher for the 62 survivors (13.3 ± 10.5 [mean ± standard deviation]) compared to the 15 nonsurvivors (7.0 ± 8.0) (P = 0.03). The fluconazole AUC/MIC (24 h) values also trended higher for survivors (775 ± 739) compared to nonsurvivors (589 ± 715) (P = 0.09). These data support the dose-dependent properties of fluconazole. Underdosing fluconazole against less-susceptible Candida isolates has the potential to increase the risk of mortality associated with candidemia.

* Corresponding author. Mailing address: Texas Medical Center, University of Houston, 1441 Moursund Street, Houston, TX 77030. Phone: (713) 795-8386. Fax: (713) 795-8383. E-mail: kgarey{at}uh.edu.

{triangledown} Published ahead of print on 13 November 2006.

Antimicrobial Agents and Chemotherapy, January 2007, p. 35-39, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00474-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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