Late-onset Sepsis in Preterm Infants Can Be Detected Preclinically by Fecal Volatile Organic Compound Analysis: A Prospective, Multicenter Cohort Study
Berkhout, Daniel J C; van Keulen, Britt J; Niemarkt, Hendrik J; Bessem, Jet R; de Boode, Willem P; Cossey, Veerle; Hoogenes, Neil; Hulzebos, Christiaan V; Klaver, Ellen; Andriessen, Peter; van Kaam, Anton H; Kramer, Boris W; van Lingen, Richard A; Schouten, Aaron; van Goudoever, Johannes B; Vijlbrief, Daniel C; van Weissenbruch, Mirjam M; Wicaksono, Alfian N; Covington, James A; Benninga, Marc A; de Boer, Nanne K H; de Meij, Tim G J
(2019) Clinical Infectious Diseases, volume 68, issue 1, pp. 70 - 77
(Article)
Abstract
Background: The intestinal microbiota has increasingly been considered to play a role in the etiology of late-onset sepsis (LOS). We hypothesize that early alterations in fecal volatile organic compounds (VOCs), reflecting intestinal microbiota composition and function, allow for discrimination between infants developing LOS and controls in a preclinical stage. Methods:
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In 9 neonatal intensive care units in the Netherlands and Belgium, fecal samples of preterm infants born at a gestational age ≤30 weeks were collected daily, up to the postnatal age of 28 days. Fecal VOC were measured by high-field asymmetric waveform ion mobility spectrometry (FAIMS). VOC profiles of LOS infants, up to 3 days prior to clinical LOS onset, were compared with profiles from matched controls. Results: In total, 843 preterm born infants (gestational age ≤30 weeks) were included. From 127 LOS cases and 127 matched controls, fecal samples were analyzed by means of FAIMS. Fecal VOCs allowed for preclinical discrimination between LOS and control infants. Focusing on individual pathogens, fecal VOCs differed significantly between LOS cases and controls at all predefined time points. Highest accuracy rates were obtained for sepsis caused by Escherichia coli, followed by sepsis caused by Staphylococcus aureus and Staphylococcus epidermidis. Conclusions: Fecal VOC analysis allowed for preclinical discrimination between infants developing LOS and matched controls. Early detection of LOS may provide clinicians a window of opportunity for timely initiation of individualized therapeutic strategies aimed at prevention of sepsis, possibly improving LOS-related morbidity and mortality.
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Keywords: high-field asymmetric waveform ion mobility spectrometry, neonatology, electronic nose, volatile organic compound, late-onset sepsis, Prospective Studies, Diagnostic Tests, Routine/methods, Humans, Male, Volatile Organic Compounds/analysis, Netherlands, Belgium, Infant, Premature, Neonatal Sepsis/diagnosis, Female, Feces/chemistry, Spectrum Analysis/methods, Infant, Newborn, Microbiology (medical), Infectious Diseases, Research Support, Non-U.S. Gov't, Multicenter Study, Journal Article, Evaluation Studies
ISSN: 1058-4838
Publisher: Oxford University Press
Note: Funding Information: Disclaimer. None of the coauthors received an honorarium, grant or other form of payment for the production of this manuscript Funding. This work was supported by unrestricted grants from the Maag Lever Darm Stichting, Landelijke Vereniging van Crematoria (Dr. C.J. Vaillant Fonds), Zeldzame Ziekte Fonds and Christine Bader Stichting Irene Kinderziekenhuis. Publisher Copyright: © 2018 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.
(Peer reviewed)