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Empirical Anti-Candida Therapy among Selected Patients in the Intensive Care Unit: A Cost-Effectiveness Analysis
- Yoav Golan, MD;
- Michael P. Wolf, MD;
- Stephen G. Pauker, MD;
- John B. Wong, MD; and
- Susan Hadley, MD
Abstract
Background: Mortality from invasive candidiasis is high. Low culture sensitivity and treatment delay contribute to increased mortality, but nonselective early therapy may result in excess costs and drug resistance.
Objective: To determine the cost-effectiveness of anti-Candida strategies for high-risk patients in the intensive care unit (ICU).
Design: Cost-effectiveness decision model.
Data Sources: Published data to 10 May 2005, identified from MEDLINE and Cochrane Library searches, ICU databases, expert estimates, and actual hospital costs.
Target Population: Patients in the ICU with suspected infection who have not responded to antibacterial therapy.
Time Horizon: Lifetime.
Perspective: Societal.
Interventions: Fluconazole, caspofungin, amphotericin B, or lipid formulation of amphotericin B given as either empirical or culture-based therapy and no anti-Candida therapy.
Outcome Measures: Incremental life expectancy and incremental cost per discounted life-year (DLY) saved.
Results of Base-Case Analysis: Ten percent of the target population will have invasive candidiasis. Empirical caspofungin therapy is the most effective strategy but is expensive ($295 115 per DLY saved). Empirical fluconazole therapy is the most reasonable strategy ($12 593 per DLY saved) and decreases mortality from 44.0% to 30.4% in patients with invasive candidiasis and from 22.4% to 21.0% in the overall target cohort.
Results of Sensitivity Analysis: Empirical fluconazole therapy is reasonable for likelihoods of invasive candidiasis greater than 2.5% or fluconazole resistance less than 24.0%. For higher resistance levels, empirical caspofungin therapy is preferred. For low prevalences of invasive candidiasis, culture-based fluconazole is reasonable. For prevalences exceeding 60%, empirical caspofungin therapy is reasonable. For caspofungin to be reasonable at a prevalence of 10%, its cost must be reduced by 58%.
Limitations: Less severe illness and limited use of broad-spectrum antimicrobial agents, typical of smaller hospitals, could result in a lower risk for invasive candidiasis.
Conclusions: In patients in the ICU with suspected infection who have not responded to antibiotic treatment, empirical fluconazole should reduce mortality at an acceptable cost. The use of empirical strategies in low-risk patients is not justified.
Article and Author Information
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Note: This paper was presented in part at the 31st Congress of The Society of Critical Care Medicine, San Diego, California, 26-30 January 2002.
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Acknowledgments: The authors thank Jerome Wilson, MA, PhD; Yehuda Carmeli, MD; and Corrado Marini, MD, for their contribution to this work, and Debra Poutsiaka, MD, for reviewing this manuscript.
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Grant Support: In part by Pfizer Inc. and the National Library of Medicine (T15 LM07092-11).
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Potential Financial Conflicts of Interest: Consultancies: S. Hadley (Schering-Plough); Honoraria: Y. Golan (Cubist Pharmaceuticals, Wyeth, Merck & Co. Inc.); J.B. Wong (Schering-Plough, National Library of Medicine, National Institute of Drug Abuse, Agency for Healthcare Research and Quality), S. Hadley (Merck & Co. Inc., Pfizer Inc.); Grants received: J.B. Wong (National Library of Medicine, National Institute of Drug Abuse, Agency for Healthcare Research and Quality, Schering-Plough), S. Hadley (Astellas Pharma, Pfizer Inc.).
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Requests for Single Reprints: Yoav Golan, MD, Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, 750 Washington Street, Box 041, Boston, MA 02111; e-mail, ygolan{at}tufts-nemc.org.
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Current Author Addresses: Drs. Golan and Hadley: Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Box 041, 750 Washington Street, Boston, MA 02111.
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Dr. Wolf: 613 Woodhills Drive, Goshen, NY 10924.
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Dr. Pauker: Department of Medicine, Tufts-New England Medical Center, 750 Washington Street, Boston, MA 02111.
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Dr. Wong: Division of Clinical Decision Making, Informatics, and Telemedicine, Tufts-New England Medical Center, 750 Washington Street, Boston, MA 02111.
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Author Contributions: Conception and design: Y. Golan, M.P. Wolf, S.G. Pauker, J.B. Wong, S. Hadley.
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Analysis and interpretation of the data: Y. Golan, M.P. Wolf, S.G. Pauker, J.B. Wong, S. Hadley.
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Drafting of the article: Y. Golan, S.G. Pauker, J.B. Wong, S. Hadley.
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Critical revision of the article for important intellectual content: Y. Golan, M.P. Wolf, S.G. Pauker, J.B. Wong, S. Hadley.
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Final approval of the article: Y. Golan, M.P. Wolf, S.G. Pauker, J.B. Wong, S. Hadley.
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Provision of study materials or patients: Y. Golan.
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Statistical expertise: Y. Golan, S.G. Pauker, J.B. Wong.
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Obtaining of funding: Y. Golan, J.B. Wong, S. Hadley.
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Administrative, technical, or logistic support: Y. Golan, J.B. Wong.
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Collection and assembly of data: Y. Golan.
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