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To evaluate the effect of prophylactic fluconazole for very low birth weight infants (VLBWI) in a neonatal intensive care unit (NICU) with a 7.8% incidence of invasive candidiasis (IC).

Interventional pre-post cohort study comparing 2 years with and without fluconazole prophylaxis protocol (2016–2018 = 228 infants and 2019–2021 = 125 infants). Fluconazole was administered to all extremely low birth weight infants (ELBWI) and infants with BW 1001–1500 g with risk factors or positive carrier cultures. Liver function tests were performed weekly.

The incidence of IC decreased from 7.8% to 2.4% (OR:0.3, p = 0.05) with the use of prophylactic fluconazole for VLBWI and in ELBWI decreased from 16,7% to 3,7% (OR:0.1, p = 0.04). No significant differences were seen in mortality.

Fluconazole is a safe, effective, and feasible strategy to prevent IC in a Latin American country.