Updates in the Pharmacologic Prophylaxis and Treatment of Invasive Candidiasis in the Pediatric and Neonatal Intensive Care Units

Abstract

Purpose of review The goal of this review was to provide an update on the prevention and treatment options for invasive candidiasis (IC) in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU). Recent findings Studies have further validated the use of fluconazole for IC prophylaxis among high-risk patients in the NICU. It remains unclear if prophylaxis leads to resistance development and the ideal dosage regimen is still not clear. Recent studies have been published comparing caspofungin and micafungin to amphotericin B and illustrated similar efficacy outcomes in the NICU. Micafungin now has approval from the United States Food and Drug Administration (FDA) for use in infants < 4 months of age. Prophylactic strategies in the PICU could include zinc and vitamin D. Anidulafungin has recent non-comparative data supporting use in pediatric patients older than 1 month of age and also has a recent FDA approval for use in children 1 month of age and older. Summary Fluconazole prophylaxis remains a reasonable strategy in select NICU patients, although further analyses of resistance and the optimal dosage regimen are needed. Echinocandins are potential therapeutic options for non-meningitis or urinary tract infections in both the neonatal and pediatric population.

Risk Factors, Diagnosis, and Treatment of Neonatal Fungal Liver Abscess: A Systematic Review of the Literature

“…Prophylactic fluconazole and oral nystatin have both proven to be successful in the prevention of neonatal IFI. Although there is robust evidence supporting the effective and safe use of fluconazole as antifungal prophylaxis, concerns regarding the potential development of antifungal resistance limits its universal use [ 44 ]. A recent nationwide retrospective study in Japan reported that only 43% of medical facilities routinely prescribed antifungal prophylaxis for high-risk neonates [ 45 ].…”

Plasma and Cerebrospinal Fluid Concentrations of Micafungin Administered at High Doses in Critically Ill Infants with Systemic Candidiasis: A Pooled Analysis of Two Studies

“…To date, Amphotericin B deoxycholate or liposomal amphotericin B are recommended as first-line therapies for invasive fungal infections in neonates, but their use can be limited by nephrotoxicity [ 18 ]. Fluconazole is recommended as a second-line drug, but hepatotoxicity and azole resistance can limit its use [ 16 , 19 ]; furthermore, fluconazole prophylaxis is recommended against invasive candidiasis in very low and extremely low-birth-weight preterm neonates or in those carriers of central venous catheters [ 20 , 21 , 22 , 23 ]. When a fungal infection is suspected in a neonate who is already receiving fluconazole, a different salvage therapy is needed.…”

“…To date, micafungin is the only echinocandin that has been approved by the European Medicines Agency (EMA) for use in neonates [ 17 ] and, as explained, recently it has also been approved by the US Food and Drug Administration (FDA) for use in infants less than four months old [ 23 ].…”

Antifungal Stewardship Programs in Children: Challenges and Opportunities

“…Current data on the appropriateness and benefits of neonatal antifungal prophylaxis suggest a more optional, customized and risk-based approach in NICUs. 13…”

“…11 Current evidence on the association between the use of antifungal prophylaxis in neonates and subsequent development of antifungal resistance is hampered by differences in local fungal epidemiology and study methodologies (ie, sample size). 13…”