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Pediatric Candidemia Epidemiology and Morbidities

A Nationwide Cohort

Lausch, Karen Rokkedal, MD*; Schultz Dungu, Kia Hee, MD; Callesen, Michael Thude, MD, PhD; Schrøder, Henrik, MD, PhD§; Rosthøj, Steen, MD, PhD; Poulsen, Anja, MD, PhD; Østergaard, Lars, MD, PhD*; Mortensen, Klaus Leth, MD, PhD*; Storgaard, Merete, MD, PhD*; Schønheyder, Henrik Carl, MD, DMSc‖,**; Søgaard, Mette, PhD††,‡‡; Arendrup, Maiken Cavling, MD, PhD, DMSc§§,¶¶,‖‖

The Pediatric Infectious Disease Journal: May 2019 - Volume 38 - Issue 5 - p 464–469
doi: 10.1097/INF.0000000000002207
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Background: Candidemia is the most frequent pediatric fungal infection, but incompletely elucidated in population-based settings. We performed a nationwide cohort study including all pediatric patients with candidemia in Denmark from 2004 to 2014 to determine age, incidence, species distribution, underlying diseases, patient management and outcomes.

Methods: All candidemia episodes were identified through the active nationwide fungemia surveillance program. Susceptibility testing followed the EUCAST E.Def 7 (European Committee on Antifungal Susceptibility Testing, Edition Definitive) reference method. χ2 test, Fisher exact test and Venn diagrams were used for statistical analyses.

Results: One hundred fifty-three pediatric patients (≤ 15 years) with 158 candidemia episodes were identified. The overall annual incidence rate was 1.3/100,000 population, higher for neonates (5.7/100,000 live births) and low birth weight neonates (103.8/100,000 live births). From 2004 to 2009 to 2010 to 2014, the proportion of Candida albicans decreased from 74.4% to 64.7%, whereas fluconazole resistance increased from 7.8% to 17.7%. Virtually all patients had at least 1 underlying disease (98.6%) and multimorbidity was common (43.5%, ≥2 underlying diseases). Underlying diseases differed by age with heart malformations and gastrointestinal disease prevalent in children younger than 3 years. The overall 30-days mortality was 10.2% and highest for neonates (17.1%). Mortality increased from 2004 to 2010 to 2014, driven by an increase among older children.

Conclusion: This first nationwide epidemiologic study of pediatric candidemia confirmed a high incidence among neonates and a substantial burden of comorbidities. Moreover, an increasing proportion of fluconazole resistant nonalbicans species was observed. Our findings underline the importance of choosing correct treatment and continuous surveillance of pediatric candidemia.

From the *Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark

Department of Pediatric and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark

Department of Pediatric, Odense University Hospital, Odense, Denmark

§Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

Department of Pediatric, Aalborg University Hospital

Department of Clinical Microbiology, Aalborg University Hospital

**Department of Clinical Medicine, University of Aalborg

††Department of Cardiology, Aalborg University Hospital

‡‡Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

§§Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital

¶¶Unit of Mycology, Statens Serum Institute, Copenhagen

‖‖Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Accepted for publication August 30, 2018.

Supported by an educational grant via the Gilead Nordic Fellowship Programme.

K.R.L. reports research grant and speakers honoraria from Gilead outside the submitted work; L.Ø. reports grants from Gilead and Pfizer outside the submitted work; K.L.M. reports grants from Pfizer, personal fees from Astra Zeneca and Horizon Pharmaceuticals outside the submitted work; M.S. reports grant from MSD (Merck, Sharp and Dohme Corp) and Gilead outside the submitted work; H.C.S. reports travel grants from MSD outside the submitted work; M.C.A. reports grants from Amplyx, Basilea, Cidara, F2G, Gilead, personal fees from Astellas, Basilea, Gilead, MSD, Pfizer, T2Biosystems, outside the submitted work. The other authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Address for correspondence: Karen Rokkedal Lausch, MD, Department of Infectious Diseases, Q Research, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark. E-mail: karelaus@rm.dk.

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