title: 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.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, AL 35294-0006, USA. jbaddley@uab.edu.
authors.forename: John W
authors.initials: JW
authors.lastname: Baddley
authors.forename: Mukesh
authors.initials: M
authors.lastname: Patel
authors.forename: Sujata M
authors.initials: SM
authors.lastname: Bhavnani
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Moser
authors.forename: David R
authors.initials: DR
authors.lastname: Andes
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002175:Candida / Q000145:classification / Q000187:drug effects*; D002177:Candidiasis / Q000382:microbiology / Q000401:mortality*; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016469:Fungemia / Q000382:microbiology / Q000401:mortality*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole