To investigate the preventive effect of topical nonabsorbable gastrointestinal antifungal prophylaxis on the incidence of fungal infection in critically ill immunocompetent patients.
Randomized controlled studies involving critically ill pediatric and adult patients in different languages from the Cochrane Controlled Trial Register (2004, issue 1), EMBASE, and MEDLINE databases (1966 to 30 April 2004) were included. Studies evaluating absorbable antifungal prophylaxis were excluded. Two reviewers assessed the quality of the studies and performed data extraction independently.
Amphotericin B and nystatin were used as the nonabsorbable antifungal prophylaxis in the 15 studies included in this meta-analysis. Ten studies used a concomitant systemic antibiotic and four more studies used concomitant topical nonabsorbable antibiotics in the treatment group. Only one study compared topical nonabsorbable antifungal prophylaxis alone with placebo. The total incidence of fungal infections (relative risk [RR], 0.30; 95% confidence interval [CI], 0.18–0.48; p < .00001; extent of inconsistency [I2] = 0%) and proportion of patients with fungal infection (RR, 0.50; 95% CI, 0.28–0.87; p = .02; I2 = 0%) were significantly reduced with topical nonabsorbable antifungal prophylaxis. The incidence of fungal urinary tract infection was significantly reduced (RR, 0.27; 95% CI, 0.10–0.74; p = .01; I2 = 0%) but not fungal pneumonia (RR, 0.57; 95% CI, 0.28–1.16; p = .12; I2 = 0%). Fungemia and catheter-related fungal sepsis were rare and not significantly reduced with nonabsorbable antifungal prophylaxis. The results remained unchanged in the sensitivity analyses after exclusion of studies with unclear study quality or exclusion of the contribution of fungal urinary tract infections to the total incidence of fungal infections.
In critically ill immunocompetent patients who are at high risk of fungal infection, topical nonabsorbable gastrointestinal antifungal prophylaxis was associated with a reduced incidence of urinary fungal infections and a trend toward reduction in respiratory fungal infections and fungemia. Limitations in study data are such that many of these infections may have represented superficial infections of uncertain clinical importance; a large, randomized, controlled trial is needed to assess the cost-effectiveness and safety of topical nonabsorbable antifungal prophylaxis in critically ill patients.
From the Department of Intensive Care, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
This study was funded solely by the Department of Intensive Care, Royal Perth Hospital. None of the authors have any financial interests to disclose.