Strategies to Prevent Invasive Candidal Infection in Extremely Preterm Infants

The highest incidence of invasive candidal infection (ICI) occurs in extremely preterm infants (<1000 g birth weight and <27 weeks' gestation). In this population, ICI has high mortality, leads to significant neurodevelopmental impairment, and results in increased length of hospital stay and costs. Randomized clinical trials in infants of less than 1000 g birth weight have demonstrated that ICI is decreased 88% by antifungal prophylaxis with fluconazole compared to 54% by nystatin prophylaxis from retrospective studies. Fluconazole is more efficacious than nystatin prophylaxis in infants weighing less than 1000 g, is less expense, requires less frequent dosing (twice weekly intravenous [IV] dosing), and can be given when infants are not feeding. While antifungal prophylaxis is inexpensive, cost-effective, and easy to administer, yet has not been instituted universally despite A-1 evidence from single and multicenter studies demonstrating efficacy and safety. Debate is ongoing over whether empiric therapy or improved infection control practices are superior to prophylaxis, whether prophylaxis should be instituted only in neonatal intensive care units (NICUs) with a relatively high ICI rate, and whether fluconazole prophylaxis is safe or risks emergence of resistance. To date, azole resistance has not emerged with targeted treatment of high-risk infants for the duration of IV catheter use. Empiric therapy for suspected ICI and standardized therapy for candidemia, including central venous catheter removal, may decrease mortality; however, these approaches still risk neurodevelopmental impairment in ICI survivors. Infection control practices have not been subjected to prospective or randomized trials to demonstrate efficacy in reducing fungal infections. Evidence is presented in this article from clinical trials demonstrating efficacy and safety of antifungal prophylaxis in preventing ICI in preterm infants. The greatest impact of antifungal prophylaxis preventing ICI and decreasing Candida-related mortality and neurodevelopmental impairment would be achieved with a universal approach in all NICUs.