Antifungal prophylaxis: identification of preterm neonates at high risk for invasive fungal infection.

We read with great interest the article by Healy et al,1 who evaluated the impact of fluconazole prophylaxis (FP) for extremely low birth weight infants on invasive candidiasis (IC) incidence, IC-related mortality rates, and fluconazole susceptibility of Candida isolated. We wish to make some comments thereon. Healy et al1 demonstrated a decrease of IC in NICU infants, after the introduction of FP, from 0.6% to 0.3%, and a 3.6 fold decrease in ELBW infants. Recent studies have demonstrated that prophylactic use of fluconazole is effective in reducing the incidence of fungal colonization and fungal systemic infections in preterm neonates.2,3 However, because of the lack of larger multicenter randomized trials and data on long term neurodevelopment outcomes as well as concern about unwanted side effects and development of Candida resistance, FP in high risk infants remains controversial. For these reasons, selecting only those infants at highest risk for IC may delay or prevent the emergence of resistance. In recent studies, the criteria chosen to identify “the high-risk neonate” were <1500 g birth weight (BW) and the presence of a central vascular catheter or endotracheal tube.4 These criteria seem to be too wide, because they could regard almost all the population sheltered in a NICU. In our NICU, FP as well as antibiotic prophylaxis did not exist, and Candida-related mortality was nearly 20% in extremely low birth weight infants. To prevent IC, we introduced a protocol of Candida surveillance cultures from stool and bronchoalveolar lavage fluid in intubated infants, and every infant who developed IC was identified and IC-related mortality was eliminated.5 All neonates with IC had a BW of <1000 g, and 15 (94%) of 16 had a gestational age of <27 weeks. Therefore, from our data, neonates with a gestational age of <27 weeks and BW of <1000 g represent the “preterm subpopulation” that would benefit most from FP. A more-precise identification of the higher-risk neonates in the NICU would be a prelude to the elaboration of more-effective prophylactic measures and should delay or prevent the emergence of resistance. Indeed, the critical question will be to find the corrected age when the immune system can face up to Candida spp to develop effective preventive strategies. Our data provide evidence that the age is somewhere around >27 weeks.