This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Baddley, J. W.
Right arrow Articles by Andes, D. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baddley, J. W.
Right arrow Articles by Andes, D. R.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2008, p. 3022-3028, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00116-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Association of Fluconazole Pharmacodynamics with Mortality in Patients with Candidemia{triangledown}

John W. Baddley,1,3* Mukesh Patel,1,3 Sujata M. Bhavnani,4 Stephen A. Moser,2 and David R. Andes5

Department of Medicine, Division of Infectious Diseases,1 Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama,2 Birmingham Veterans Administration Medical Center, Birmingham, Alabama,3 Institute for Clinical Pharmacodynamics, Ordway Research Institute, Albany, New York,4 Department of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin5

Received 25 January 2008/ Returned for modification 21 March 2008/ Accepted 23 June 2008

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 ≥64 µg/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 ≥64 was associated with increased patient mortality (P ≤ 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.

* Corresponding author. Mailing address: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, 1900 University Boulevard, 229 Tinsley Harrison Tower, Birmingham, AL 35294-0006. Phone: (205) 934-5191. Fax: (205) 934-5155. E-mail: jbaddley{at}uab.edu

{triangledown} Published ahead of print on 30 June 2008.

Antimicrobial Agents and Chemotherapy, September 2008, p. 3022-3028, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00116-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kuper, K. M., Hirsch, E. B., Tam, V. H., on behalf of the Houston Infectious Diseases Netwo, (2009). Significant publications on infectious diseases pharmacotherapy in 2008. Am J Health Syst Pharm 66: 1726-1734 [Abstract] [Full Text]  
  • Pfaller, M. A., Messer, S. A., Hollis, R. J., Boyken, L., Tendolkar, S., Kroeger, J., Diekema, D. J. (2009). Variation in Susceptibility of Bloodstream Isolates of Candida glabrata to Fluconazole According to Patient Age and Geographic Location in the United States in 2001 to 2007. J. Clin. Microbiol. 47: 3185-3190 [Abstract] [Full Text]  
  • Arendrup, M. C., Cuenca-Estrella, M., Donnelly, J. P., Lass-Florl, C., Rodriguez-Tudela, J. L., Baddley, J. W., Ostrosky-Zeichner, L., Bhavnani, S. M., Andes, D. R. (2009). Association of Fluconazole Pharmacodynamics with Mortality in Patients with Candidemia. Antimicrob. Agents Chemother. 53: 2704-2706 [Full Text]  
  • Pfaller, M. A., Boyken, L. B., Hollis, R. J., Kroeger, J., Messer, S. A., Tendolkar, S., Diekema, D. J. (2008). Validation of 24-Hour Fluconazole MIC Readings versus the CLSI 48-Hour Broth Microdilution Reference Method: Results from a Global Candida Antifungal Surveillance Program. J. Clin. Microbiol. 46: 3585-3590 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»