Association of fluconazole pharmacodynamics with mortality in patients with candidemia.

Abstract

Recent studies of nonneutropenic 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. We assessed the impact of MICs for Candida, fluconazole pharmacodynamics, and patient characteristics on all-cause mortality with use of a prospective cohort of 96 hospitalized patients with candidemia. Among 84 patients for whom Candida isolates were available for testing, the most frequent Candida species isolated were Candida albicans (44%), followed by Candida parapsilosis (20.2%), and Candida glabrata (20.2%). Fluconazole resistance (MIC of >or=64 microg/ml) was present in 7 (8.3%) to 10 (11.9%) of 84 isolates, depending on the MIC endpoint determination method (50% or 80% inhibition read at 24 or 48 h). Overall mortality occurred in 27 (28.1%) of 96 patients, and nonsurvivors were more likely to have fluconazole-resistant isolates (25% versus 6.7%; P = 0.02). Multivariable analysis demonstrated an association between fluconazole resistance and mortality, but it did not reach statistical significance (odds ratio, 5.3; 95% confidence interval, 0.8 to 33.4; P = 0.08). By pharmacodynamic analysis, a fluconazole area under the concentration-time curve/MIC of <11.5 or MIC of >or=64 was associated with increased patient mortality (P <or= 0.09). These data support previous findings of an antifungal exposure-response relationship to mortality in patients with candidemia. In addition, similar MICs were obtained using a 24- or 48-h MIC endpoint determination, thus providing the opportunity to assess earlier the impact of isolate susceptibility on therapy.

• Authors: John W Baddley, Mukesh Patel, Sujata M Bhavnani, Stephen A Moser, David R Andes
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 52 Issue 9 Pg. 3022-8 (Sep 2008) ISSN: 1098-6596 [Electronic] United States
• PMID: 18591269 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Fluconazole

Topics

• APACHE
• Adult
• Aged
• Antifungal Agents (administration & dosage, pharmacology, therapeutic use)
• Candida (classification, drug effects)
• Candidiasis (microbiology, mortality)
• Dose-Response Relationship, Drug
• Drug Resistance, Fungal
• Female
• Fluconazole (administration & dosage, pharmacology, therapeutic use)
• Fungemia (microbiology, mortality)
• Humans
• Logistic Models
• Male
• Microbial Sensitivity Tests
• Middle Aged
• Survival Analysis