Clinical trials of antifungal prophylaxis among patients in surgical intensive care units: concepts and considerations.

BACKGROUND Fungal infections are important clinical infections in patients in surgical intensive care units. In some institutions, antifungal prophylaxis has become commonplace, and increasing resistance has been reported. However, trials of antifungal prophylaxis are hampered by difficulties in trial design, and the findings may not be generalizable. METHODS Issues in clinical trial design are reviewed from existing and theoretical perspectives. RESULTS Identification of a primary hypothesis with a sound epidemiological basis is essential. The study must include institutions where fungal infections have a high and well-studied incidence. A high-risk patient population should be identified and enrolled. The agent selected should have an appropriate spectrum, be easily delivered to the population selected, and be cost effective with few adverse events. At present, fluconazole appears to be the best agent for targeted prophylaxis. The primary end point of the study should be based on an easily measured outcome, for example, days free from fungal infection rather than death due to fungal infection. CONCLUSIONS Trials of antifungal prophylaxis for patients in surgical intensive care units have had problems in design, and several issues in the conceptual basis of future clinical trials must be addressed.