Fluconazole Prophylaxis in High-Risk Neonates

Abstract

OBJECTIVE To evaluate the literature regarding the use of fluconazole prophylaxis in high-risk neonates. DATA SOURCES Literature was accessed through MEDLINE (February 2001-August 2009) using the search terms fluconazole and prophylaxis, with limits for age group (ie, birth-18 y). Reference citations from identified articles were also reviewed. DATA SELECTION AND DATA EXTRACTION All prospective and retrospective studies in English identified from MEDLINE were evaluated. DATA SYNTHESIS Critically ill neonates possess a number of risk factors that predispose them to fungal colonization with Candida spp. In many cases, colonization may progress to invasive systemic infections despite efforts aimed at early diagnosis and treatment. Because of its success among immunocompromised patients, fluconazole prophylaxis has been suggested as a possible approach for reducing the rates of both colonization and invasive fungal infections among at-risk neonates. To date, 4 prospective randomized controlled trials and 8 retrospective cohort studies have examined fluconazole prophylaxis in neonates. Although fluconazole prophylaxis appears to reduce the rates of colonization and invasive fungal infections, no trial in this review was able to demonstrate a significant difference in long-term morbidity or mortality. Concerns also remain regarding the adverse effects associated with prolonged exposure to fluconazole therapy. Lack of standardized study designs and treatment regimens also limit widespread recommendation for the use of fluconazole prophylaxis in clinical practice. CONCLUSIONS While it may be beneficial for critically ill neonates with certain predisposing risk factors (eg, central venous access, sustained exposure to broad-spectrum antibiotics, or units with significantly high incidence of invasive fungal infections), existing research does not support the use of fluconazole prophylaxis based on birth weight or gestational age alone. Multifactor analysis evaluating the effect of fluconazole prophylaxis is necessary to establish which neonates would benefit from this practice.