TY - JOUR
T1 - Late-onset sepsis in preterm infants can be detected preclinically by fecal volatile organic compound analysis
T2 - A prospective, multicenter cohort study
AU - Berkhout, Daniel J.C.
AU - Van Keulen, Britt J.
AU - Niemarkt, Hendrik J.
AU - Bessem, Jet R.
AU - De Boode, Willem P.
AU - Cossey, Veerle
AU - Hoogenes, Neil
AU - Hulzebos, Christiaan V.
AU - Klaver, Ellen
AU - Andriessen, Peter
AU - Van Kaam, Anton H.
AU - Kramer, Boris W.
AU - Van Lingen, Richard A.
AU - Schouten, Aaron
AU - Van Goudoever, Johannes B.
AU - Vijlbrief, Daniel C.
AU - Van Weissenbruch, Mirjam M.
AU - Wicaksono, Alfian N.
AU - Covington, James A.
AU - Benninga, Marc A.
AU - De Boer, Nanne K.H.
AU - De Meij, Tim G.J.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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. 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.
AB - 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. 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.
KW - electronic nose
KW - high-field asymmetric waveform ion mobility spectrometry
KW - late-onset sepsis
KW - neonatology
KW - volatile organic compound
UR - http://www.scopus.com/inward/record.url?scp=85052623810&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/cid/ciy383
DO - https://doi.org/10.1093/cid/ciy383
M3 - Article
C2 - 29931245
SN - 1058-4838
VL - 68
SP - 70
EP - 77
JO - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
IS - 1
ER -