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Antimicrob. Agents Chemother. doi:10.1128/AAC.00474-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Association of Fluconazole AUC/MIC and Dose/MIC Ratios with Mortality in Non-neutropenic Patients with Candidemia

University of New Mexico, Albuquerque, NM, Merck & Co., West Point PA, West Point PA, Jefferson Medical College, Philadelphia, PA University of Houston, Houston, TX

^* To whom correspondence should be addressed. Email: kgarey{at}uh.edu.

	Abstract

The current study tested in vitro susceptibility of Candida bloodstream isolates to fluconazole to determine if the ratio of fluconazole area under the concentration-time cure (AUC) or weight normalized daily dose (Dose) to MIC correlated with mortality. Fluconazole susceptibility and outcome data were determined for 77 patients with a positive Candida blood culture between 2002-2005. 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 C. albicans (16.3%), C. glabrata (36.4%), C. parapsilosis (0%), C. tropicalis (0%), and C. lusitaniae (33.3%). A mortality rate of 50% was noted among patients infected with non-susceptible (MIC 16 µg/mL) compared to 18% for patients infected with susceptible (MIC 8 µg/mL) isolates (p=0.17). The fluconazole Dose/MIC (24 hour) values were significantly higher in the 62 survivors (13.3 ± 10.5 (mean ± SD)) compared to the 15 non-survivors (7.0 ± 8.0) (p=0.03). The fluconazole AUC/MIC (24 hour) values also trended higher for survivors (775 ± 739) compared to non-survivors (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.

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