Fluconazole Doses Used for Prophylaxis of Invasive Fungal Infection in Neonatal Intensive Care Units: A Network Meta-Analysis

• Published in: The Journal of pediatrics Vol. 185; pp. 129 - 135.e6
• Main Authors: Leonart, Letícia Paula, MSc, Tonin, Fernanda Stumpf, MSc, Ferreira, Vinicius Lins, MSc, Tavares da Silva Penteado, Suelem, MSc, de Araújo Motta, Fábio, PhD, Pontarolo, Roberto, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2017
• Subjects: Antifungal Agents - administration & dosage; Candidiasis, Invasive - prevention & control; dose; Dose-Response Relationship, Drug; fluconazole; Fluconazole - administration & dosage; Humans; Intensive Care Units, Neonatal; neonate, preterm infant; Network Meta-Analysis; Pediatrics; prophylaxis; RCT; Invasive candidiasis; VLBW; Very low birth weight; Invasive fungal infection; NICU; prophylaxis; IFI; Randomized controlled trial; Pharmacokinetic; fluconazole; dose; Neonatal intensive care unit; Credible interval; IC; CrI; PK; neonate, preterm infant
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2017.02.039

Objectives To evaluate the safety and efficacy of different doses of fluconazole used for invasive prophylaxis of fungal infection in neonates. Study design A systematic search was conducted with PubMed, Scopus, and Web of Science. A manual search was performed as well. Only randomized controlled trials of neonates in a neonatal intensive care unit (NICU) who received fluconazole prophylaxis for invasive fungal infection, regardless of the dose or therapeutic regimen, were included in this review. Data on baseline characteristics, outcomes incidence of proven invasive Candida infection, overall mortality, and invasive Candida infection-related mortality were extracted. Results Eleven studies were included in the review, with fluconazole doses of 3, 4, or 6 mg/kg. When the incidence of invasive Candida and invasive Candida -related mortality were considered as outcomes, the 3 and 6 mg/kg fluconazole doses were found to be statistically superior to placebo (OR, 5.48 [95% credible interval, 1.81-18.94] and 2.63 [1.18-7.02], respectively, and 15.32 [1.54-54.31] and 9.14 [1.26-142.7], respectively), but data for the 3 doses were not statistically significantly different. Conclusions Use of the lowest fluconazole dose (3 mg/kg) should be recommended for Candida prophylaxis in neonates, given that increasing the fluconazole dose is not associated with higher efficacy and has greater potential for toxicity and increased cost.