Fungal Prophylaxis in the Neonatal Intensive Care Unit

C. Mary Healy, MD^*

^* Department of Pediatrics, Baylor College of Medicine and The Woman's Hospital of Texas, Houston, Tex

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 causedeath or neurodevelopmental impairment in almost 75% of infectedextremely low-birthweight (ELBW) infants (birthweight $≤$ 1,000g). Preventive strategies are urgently needed to improve onthese poor outcomes. The antifungal agent fluconazole is anideal candidate prophylactic agent. Its pharmacokinetic propertiesand distribution allow for low doses and extended intervalswhile maintaining high tissue concentrations. In the past decade,four randomized, controlled trials and seven retrospective cohortstudies have evaluated fluconazole prophylaxis for the preventionof fungal infection in ELBW or VLBW infants. These studies haveshown that fluconazole treatment significantly reduces Candidainfection rates with a concomitant reduction in Candida-relatedmortality. To date, fluconazole prophylaxis has not been associatedwith adverse events or with the emergence of fluconazole-resistantCandida sp. Although further studies may provide informationto allow targeting of prophylaxis to infants at highest risk,fluconazole prophylaxis should be strongly considered in a time-limitedfashion, especially in neonatal intensive care units that havehigher-than-baseline rates of Candida infection, in infantsweighing less than 1,000 g at birth, and for those who havesignificant ongoing risk factors.

Abbreviations: BW: birthweight • CVC: central vascular catheter • ELBW: extremely low birthweight • FP: fluconazole prophylaxis • GA: gestational age • ICI: invasive Candida infection • IV: intravenous • NDI: neurodevelopmental impairment • NICU: neonatal intensive care unit • PN: parenteral nutrition • RCT: randomized, controlled trial • VLBW: very low birthweight