Association of fluconazole pharmacodynamics with mortality in patients with candidemia

Antimicrob Agents Chemother. 2008 Sep;52(9):3022-8. doi: 10.1128/AAC.00116-08. Epub 2008 Jun 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antifungal Agents
  • Fluconazole