Empirical Anti-Candida Therapy among Selected Patients in the Intensive Care Unit: A Cost-Effectiveness Analysis

20 December 2005 | Volume 143 Issue 12 | Pages 857-869

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.

Editors' Notes Context Invasive candidiasis has several treatments. How to balance their costs and effectiveness is not known. Contribution According to this cost-effectiveness analysis, empirical caspofungin therapy is the most effective strategy for patients in the intensive care unit (ICU) with suspected infection that has not responded to antibacterial therapy. However, because of its high cost, caspofungin is less cost-effective than empirical fluconazole (incremental cost of $295 115 vs. $12 593 per discounted life-year saved). Therapies with empirical amphotericin B and the lipid form of amphotericin (L-amphotericin) were the least effective strategies, largely because of drug toxicities. Implications The authors recommend empirical fluconazole therapy for patients in the ICU with suspected infection because it reduces mortality at an acceptable cost. —The Editors

 

Author and Article Information

From Tufts-New England Medical Center, Boston, Massachusetts.

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.

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.

Grant Support: In part by Pfizer Inc. and the National Library of Medicine (T15 LM07092-11).

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.).

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.

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.

Dr. Wolf: 613 Woodhills Drive, Goshen, NY 10924.

Dr. Pauker: Department of Medicine, Tufts-New England Medical Center, 750 Washington Street, Boston, MA 02111.

Dr. Wong: Division of Clinical Decision Making, Informatics, and Telemedicine, Tufts-New England Medical Center, 750 Washington Street, Boston, MA 02111.

Author Contributions: Conception and design: Y. Golan, M.P. Wolf, S.G. Pauker, J.B. Wong, S. Hadley.

Analysis and interpretation of the data: Y. Golan, M.P. Wolf, S.G. Pauker, J.B. Wong, S. Hadley.

Drafting of the article: Y. Golan, S.G. Pauker, J.B. Wong, S. Hadley.

Critical revision of the article for important intellectual content: Y. Golan, M.P. Wolf, S.G. Pauker, J.B. Wong, S. Hadley.

Final approval of the article: Y. Golan, M.P. Wolf, S.G. Pauker, J.B. Wong, S. Hadley.

Provision of study materials or patients: Y. Golan.

Statistical expertise: Y. Golan, S.G. Pauker, J.B. Wong.

Obtaining of funding: Y. Golan, J.B. Wong, S. Hadley.

Administrative, technical, or logistic support: Y. Golan, J.B. Wong.

Collection and assembly of data: Y. Golan.

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