Fluconazole prophylaxis for prevention of invasive fungal infections in targeted highest risk preterm infants limits drug exposure

Objective: Previous reports suggest a benefit of fluconazole prophylaxis in extremely low birth weight (ELBW) infants < 1000 g. Our aim was to evaluate if limiting fluconazole prophylaxis to targeted highest risk infants effectively prevents invasive fungal infections, has no undesired side effects and limits unnecessary drug exposure. Study Design: This nonrandomized retrospective pre-post intervention study compared two groups of infants: (1) Infants < 26 weeks gestation and/or < 750 g birth weight, requiring central vascular access and admitted to the Monroe Carell Jr Children's Hospital at Vanderbilt neonatal intensive care unit (NICU) prior to 5 days of age, who received fluconazole prophylaxis and (2) a matched control group from the year prior to prophylaxis. This target population was selected for fluconazole prophylaxis based on prior infection control data from our institution and a number needed to treat of < 15 to prevent one episode of fungemia. Following implementation and integration through the institution's computerized physician order entry (CPOE) system, provider adherence to the protocol was assessed during the prophylaxis period. Result: A total of 86 patients were included in the study, 44 in the no-prophylaxis group and 42 in the prophylaxis group. In the targeted prophylaxis group, no invasive fungal infections were observed as compared to nine infants with invasive infections in the no-prophylaxis group (P = 0.004). No significant adverse effects were recorded. Targeting the highest risk infants reduced the number of infants < 1000 g requiring prophylaxis from 80 to 42 (48% reduction) with no preventable infection missed. Provider compliance was 91% following implementation of this protocol through the CPOE system using a standardized order set. Conclusion: Targeting the highest risk infants for fluconazole prophylaxis through CPOE can effectively prevent invasive fungal infections and limit drug exposure with no unwanted side effects.