Clinical trials of antifungal prophylaxis in neonates have primarily focused on the use of fluconazole. These studies have demonstrated that prophylactic fluconazole decreased candidal colonization and invasive infection in preterm infants.[100,134–136] Fluconazole prophylaxis decreases the composite outcome of mortality and invasive fungal infections in preterm infants. In a study by Weitkamp et al., targeting fluconazole prophylaxis in only the highest risk infants (<26 weeks, <750 g and with central venous access), it was found that invasive fungal infections can be prevented and drug exposure can be limited with no unwanted side effects.
Nystatin and miconazole are local antifungal agents that are not well absorbed in the GI tract. The use of nystatin has been shown to reduce the risk of invasive candidiasis especially in VLBW infants.[138,139] By contrast, a study of 600 newborn infants admitted to the NICU with a low baseline fungal infection rate (<3%) found oral miconazole prophylaxis reduced rectal fungal colonization but did not influence systemic fungal infection. In a recent randomized controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonization and invasive fungal infection in VLBW infants, there were no differences in fungal colonization and invasive fungal infection between the nystatin and fluconazole groups. In another systematic review, both fluconazole and nystatin were effective and safe in preventing invasive fungal infections in VLBW infants. Given the paucity of data comparing fluconazole with nystatin, the choice of antifungal agent should be influenced by the incidence of invasive fungal infections, local epidemiology and relative cost.
Retrospective studies have reported conflicting results regarding the emergence of fluconazole-resistant Candida species. One study reported that fluconazole-resistant C. parapsilosis emerged in a NICU after 10 years of fluconazole prophylaxis, but other studies did not.[143–146] Cholestasis has been reported in infants receiving fluconazole prophylaxis, but there was no increase in length of parenteral nutrition, risk for NEC or long-term adverse effects in survivors. The 2009 Infectious Diseases Society of America guidelines state that prophylactic fluconazole be considered only for ELBW infants (birth weight <1000 g) who are cared for in a NICU where the baseline rate of systemic fungal infection is high (>5%).[90,91,144] The recommended regimen for ELBW neonates is fluconazole administered intravenously during the first 48–72 h after birth at a dose of 3 mg/kg, twice a week, for 4–6 weeks, or until intravenous access no longer is required for care. Before implementation of chemoprophylaxis as standard practice in a NICU, every unit should optimize its infection–prevention practices such as bundles for intravascular catheter insertion and avoid injudicious use of antimicrobial agents.
Expert Rev Anti Infect Ther. 2013;11(7):709-721. © 2013 Expert Reviews Ltd.