Efficacy of fluconazole prophylaxis for prevention of invasive fungal infection in extremely low birth weight infants

Abstract

Background: Invasive fungal infections (IFI) are an important cause of late-onset disease in extremely low birth weight (ELBW) infants. Despite prior trials of fluconazole prophylaxis in neonates, application of this regimen remains controversial. Review of our neonatal intensive care unit aggregate annual number of fungal isolates from sterile sites in ELBW infants from 1997 to 2006 suggested a significant decrease following the institution of routine prophylactic fluconazole in February 2002. We undertook a retrospective study to document the efficacy and adverse effects of routine fluconazole prophylaxis.

Methods: ELBW infants admitted during 2000 to 2006 were divided into 2 groups: Control group-admitted before the institution of fluconazole prophylaxis, and Fluconazole group-admitted after institution of fluconazole prophylaxis. Primary outcome was the frequency of IFI. Secondary outcome was the frequency of cholestasis, which has been rarely reported with fluconazole use.

Results: Data were extracted from 262 infant records: control 99, fluconazole 163. Baseline demographics and potentially confounding variables differed between the 2 groups with greater birth weight, greater gestational age, shorter durations of ventilation and central catheter use, and earlier start of feeding in the control group, reflecting healthier control infants. Frequency of IFI was 7.1% in the control group versus 1.8% in the fluconazole group, P = 0.045. Logistic regression revealed that fluconazole prophylaxis was independently associated with a lower risk of IFI. There was no difference in the frequency of cholestasis between the control and fluconazole groups.

Conclusions: Prophylactic administration of fluconazole to all ELBW infants was associated with significantly decreased rates of IFI without associated adverse effects.