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Antimicrob. Agents Chemother. doi:10.1128/AAC.00116-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Association of Fluconazole Pharmacodynamics with Mortality in Patients with Candidemia

Department of Medicine, Division of Infectious Diseases, and Department of Pathology, University of Alabama at Birmingham; Birmingham Veterans Administration Medical Center, Birmingham, Alabama; Institute for Clinical Pharmacodynamics, Ordway Research Institute, Albany, NY; Department of Medicine and Medical Microbiology and Immunology; University of Wisconsin, Madison, Wisconsin

^* To whom correspondence should be addressed. Email: jbaddley{at}uab.edu.

	Abstract

Background: Recent studies of non-neutropenic patients with candidemia or candidiasis suggest that fluconazole pharmacodynamic parameters correlate with clinical outcomes; however, additional data of correlation to mortality in patients with candidemia would be valuable.

Methods: We assessed the impact of Candida MIC, fluconazole pharmacodynamics and patient characteristics on all-cause mortality with use of a prospective cohort of 96 hospitalized patients with candidemia.

Results: Among 84 patients with Candida isolates available for testing, the most frequent Candida species isolated were C. albicans (44%), followed by C. parapsilosis (20.2%), and C. glabrata (20.2%). Fluconazole-resistance (MIC64ug/ml) was present in 7 (8.3%) to 10 (11.9%) of 84 isolates, depending on MIC endpoint determination method (50% or 80% inhibition read at 24 or 48 hours). Overall mortality occurred in 27(28.1%) of 96 patients and non-survivors were more likely to have fluconazole-resistant isolates (25% vs. 6.7%; p=0.02). Multivariable analysis demonstrated an association between fluconazole resistance and mortality, but it did not reach statistical significance (OR 5.3, 95% CI 0.8-33.4; p=0.08). By pharmacodynamic analysis, a fluconazole AUC/MIC value 11.5 or MIC value 64 was associated with increased patient mortality (p 0.09).

Conclusions: These data support previous findings of an antifungal exposure-response relationship to mortality in patients with candidemia. In addition, similar MICs were obtained using 24 or 48 hr MIC endpoint determination thus providing the opportunity to assess earlier the impact of isolate susceptibility on therapy.