Systemic Antifungal Prescribing in Neonates and Children: Outcomes from the Antibiotic Resistance and Prescribing in European Children (ARPEC) Study

J. M. Lestner*, A. Versporten, K. Doerholt, A. Warris, E. Roilides, M. Sharland, J. Bielicki, H. Goossens, ARPEC Project Group

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


The appropriate use of systemic antifungals is vital in the prevention and treatment of invasive fungal infection (IFI) in immunosuppressed children and neonates. This multicenter observational study describes the inpatient prescribing practice of antifungal drugs for children and neonates and identifies factors associated with prescribing variability. A single-day point prevalence study of antimicrobial use in hospitalized neonates and children was performed between October and December 2012. The data were entered through a study-specific Web-based portal using a standardized data entry protocol. Data were recorded from 17,693 patients from 226 centers. A total of 136 centers recorded data from 1,092 children and 380 neonates receiving at least one antifungal agent. The most frequently prescribed systemic antifungals were fluconazole (n = 355) and amphotericin B deoxycholate (n = 195). The most common indications for antifungal administration in children were medical prophylaxis (n = 325), empirical treatment of febrile neutropenia (n = 122), and treatment of confirmed or suspected IFI (n = 100 [14%]). The treatment of suspected IFI in low-birthweight neonates accounted for the majority of prescriptions in the neonatal units (n = 103). An analysis of variance (ANOVA) demonstrated no significant effect of clinical indication (prophylaxis or treatment of systemic or localized infection) on the total daily dose (TDD). Fewer than one-half of the patients (n = 371) received a TDD within the dosing range recommended in the current guidelines. Subtherapeutic doses were prescribed in 416 cases (47%). The predominance of fluconazole and high incidence of subtherapeutic doses in participating hospitals may contribute to suboptimal clinical outcomes and an increased predominance of resistant pathogenic fungi. A global consensus on antifungal dosing and coordinated stewardship programs are needed to promote the consistent and appropriate use of antifungal drugs in neonates and children.

Original languageEnglish
Pages (from-to)782-789
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Issue number2
Early online date17 Nov 2014
Publication statusPublished - Feb 2015

Bibliographical note


We thank the ARPEC Project Group members for their assistance in the collection, management, and analysis of clinical data.

This study was funded by the European Commission Health and Consumer Protection Directorate General (DG SANCO) through the Executive Agency for Health and Consumers (EAHC).

J.M.L. has received grant support from Gilead. E.R. has received research grant support from Pfizer, Gilead, Enzon, Schering, and Wyeth, has served as a consultant to Schering, Gilead, Astellas Gilead, Cephalon, and Pfizer, and has been in the speakers' bureaus of Wyeth, Schering, Merck, and Astellas. A.W. has received unrestricted research grants from Pfizer and Gilead. H.G. has received research grants from bioMérieux.




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