Candida sp are the third most common cause of late-onset sepsis (occurring at >72 hours of age) in very low-birthweight (VLBW) infants (birthweight ≤1,500 g). Invasive candidiasis may cause death or neurodevelopmental impairment in almost 75% of infected extremely low-birthweight (ELBW) infants (birthweight ≤1,000 g). Preventive strategies are urgently needed to improve on these poor outcomes. The antifungal agent fluconazole is an ideal candidate prophylactic agent. Its pharmacokinetic properties and distribution allow for low doses and extended intervals while maintaining high tissue concentrations. In the past decade, four randomized, controlled trials and seven retrospective cohort studies have evaluated fluconazole prophylaxis for the prevention of fungal infection in ELBW or VLBW infants. These studies have shown that fluconazole treatment significantly reduces Candida infection rates with a concomitant reduction in Candida-related mortality. To date, fluconazole prophylaxis has not been associated with adverse events or with the emergence of fluconazole-resistant Candida sp. Although further studies may provide information to allow targeting of prophylaxis to infants at highest risk, fluconazole prophylaxis should be strongly considered in a time-limited fashion, especially in neonatal intensive care units that have higher-than-baseline rates of Candida infection, in infants weighing less than 1,000 g at birth, and for those who have significant ongoing risk factors.

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