Antifungal Treatment and Outcome in Very-Low-Birth-Weight-Infants - A Population-Based Observational Study of the German Neonatal Network.

Antifungal Treatment and Outcome in Very-Low-Birth-Weight-Infants - A Population-Based Observational Study of the German Neonatal Network.

Pediatr Infect Dis J. 2018 Mar 29;:

Authors: Fortmann I, Hartz A, Paul P, Pulzer F, Müller A, Böttger R, Proquitté H, Dawczynski K, Simon A, Rupp J, Herting E, Göpel W, Härtel C, German Neonatal Network

Abstract
INTRODUCTION: The diagnostic proof of fungal infection in preterm infants is difficult. Antifungal treatment (AFT) is often initiated empirically when infants with suspected infection do not improve despite broad spectrum antibiotic therapy. It was the aim of our study to determine the rate of exposure to empirical AFT in a large cohort of very low birth weight infants (VLBWI) of the German Neonatal Network (GNN) and to address associated risks and outcomes.
METHODS: The epidemiological database consisted of n= 13.343 VLBWI born in 54 GNN centers between 2009 and 2015. AFT was defined as number of neonates who got any dose of at least one of the following antifungal drugs: Fluconazole, Amphotericin B, Voriconazole and Caspofungin (denominator: number of infants enrolled in GNN) for treatment (not prophylaxis) of (suspected) fungal infection. Univariate and logistic regression analyses were used to identify risk factors for exposure to AFT as well as associated short-term morbidities and long-term outcomes at 5 year-follow-up.
RESULTS: In our cohort, 724/13.343 (5.4%) VLBWI were exposed to empiric antifungal treatment, and had a mean gestational age of 25.7 (± 2.1) weeks. 44/13.343 (0.3%) had proven bloodstream infection with Candida spp. The main risk factors for exposure to AFT were gestational age, postnatal steroid treatment, need for abdominal surgery and use of carbapenems. Notably, antifungal treatment was associated with adverse outcomes such as bronchopulmonary dysplasia (BPD; adjusted OR 1.9, 95% CI 1.6-2.3, p < 0.001) and Retinopathy of prematurity requiring intervention (ROP; adjusted OR 1.69, 95% CI 1.3-2.3, p <0.001) but not mortality. In the subgroup of infants available for 5-year-follow-up (n= 895), exposure to antifungal treatment was associated with a risk for cerebral palsy (CP; adjusted OR 2.79, 95% CI 1.11-7.04, p = 0.04) and IQ < 85 (adjusted OR 2.07, 95% CI 1.01-4.28, p = 0.049).
CONCLUSION: A significant proportion of VLBWI is exposed to AFT, specifically those born < 26 weeks. Exposed infants were found to have a higher risk for adverse outcomes which may reflect their significant vulnerability in general. Given the observational design of our study, it remains unclear whether potential side effects of empirical or target antifungal treatment itself contribute to adverse outcome. Future studies need to include risk-based strategies and stewardship programs to restrict the use of antifungal management in VLBWI.

PMID: 29601449 [PubMed - as supplied by publisher]

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