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Empirical Fluconazole Doesn’t Help

In high-risk ICU patients, empirical fluconazole did not appreciably improve clinical outcomes.

Invasive candidiasis increases morbidity and mortality in patients who have prolonged ICU stays. Some small studies have shown that prophylactic use of antifungal agents can reduce the incidence of such infections and the attendant morbidity and mortality. However, this strategy treats many patients who may not be at risk for invasive candidiasis and increases the chances that drug-resistant Candida strains will emerge. But what about empirical use of such agents?

In a double-blind, multisite, manufacturer-supported study conducted between 1995 and 2000, researchers evaluated treatment success (defined as a composite of fever resolution, absence of invasive fungal infection, lack of toxicity-related treatment discontinuation, and lack of need for nonstudy antifungal treatment) in adult ICU patients at high risk for invasive candidiasis who had fever despite use of broad-spectrum antibiotics. The 270 participants were randomized to receive intravenous fluconazole (800 mg daily) or placebo. They were treated for 14 days and then followed for an additional 30 days. The success rate for the composite endpoint was 36% in the fluconazole group and 38% in the placebo group (relative risk, 0.95; 95% confidence interval, 0.69–1.32).

Comment: The authors point out that the rates of invasive fungal infection were lower than expected, and the confidence intervals were wide. Thus, they could not exclude a relative benefit for fluconazole (as defined by their composite endpoint) of 32%. Nonetheless, they interpret their results as suggesting that there is no demonstrable benefit to empirical fluconazole treatment in the ICU setting. An editorialist emphasizes that such better-than-expected outcomes are good news, because infection-control practices already in place appear to be working. He suggests that rather than putting effort into studying antifungal prophylaxis with this or other agents, we should be improving infection control and developing better tests to identify fungal infections at an earlier stage.

— Stephen G. Baum, MD

Published in Journal Watch Infectious Diseases August 6, 2008

Citation(s):

Schuster MG et al. Empirical fluconazole versus placebo for intensive care unit patients: A randomized trial. Ann Intern Med 2008 Jul 15; 149:83.

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• Medline abstract (Free)

Fekete T. The answer is in: Fluconazole prophylaxis is not beneficial for intensive care unit patients without neutropenia. Ann Intern Med 2008 Jul 15; 149:140.

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• Medline abstract (Free)