TY - JOUR
T1 - Temporal airway microbiome changes related to ventilator-associated pneumonia in children
AU - Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN)
AU - Mourani, Peter M.
AU - Sontag, Marci K.
AU - Williamson, Kayla M.
AU - Harris, J. Kirk
AU - Reeder, Ron
AU - Locandro, Chris
AU - Carpenter, Todd C.
AU - Maddux, Aline B.
AU - Ziegler, Katherine
AU - Simões, Eric A.F.
AU - Osborne, Christina M.
AU - Ambroggio, Lilliam
AU - Leroue, Matthew K.
AU - Robertson, Charles E.
AU - Langelier, Charles
AU - DeRisi, Joseph L.
AU - Kamm, Jack
AU - Hall, Mark W.
AU - Zuppa, Athena F.
AU - Carcillo, Joseph
AU - Meert, Kathleen
AU - Sapru, Anil
AU - Pollack, Murray M.
AU - McQuillen, Patrick
AU - Notterman, Daniel A.
AU - Dean, J. Michael
AU - Wagner, Brandie D.
N1 - Publisher Copyright:
Copyright ©ERS 2021
PY - 2021/3/1
Y1 - 2021/3/1
N2 - We sought to determine whether temporal changes in the lower airway microbiome are associated with ventilator-associated pneumonia (VAP) in children. Using a multicentre prospective study of children aged 31 days to 18 years requiring mechanical ventilation support for >72 h, daily tracheal aspirates were collected and analysed by sequencing of the 16S rRNA gene. VAP was assessed using 2008 Centers for Disease Control and Prevention paediatric criteria. The association between microbial factors and VAP was evaluated using joint longitudinal time-to-event modelling, matched case–control comparisons and unsupervised clustering. Out of 366 eligible subjects, 66 (15%) developed VAP at a median of 5 (interquartile range 3–5) days post intubation. At intubation, there was no difference in total bacterial load (TBL), but Shannon diversity and the relative abundance of Streptococcus, Lactobacillales and Prevotella were lower for VAP subjects versus non-VAP subjects. However, higher TBL on each sequential day was associated with a lower hazard (hazard ratio 0.39, 95% CI 0.23–0.64) for developing VAP, but sequential values of diversity were not associated with VAP. Similar findings were observed from the matched analysis and unsupervised clustering. The most common dominant VAP pathogens included Prevotella species (19%), Pseudomonas aeruginosa (14%) and Streptococcus mitis/pneumoniae (10%). Mycoplasma and Ureaplasma were also identified as dominant organisms in several subjects. In mechanically ventilated children, changes over time in microbial factors were marginally associated with VAP risk, although these changes were not suitable for predicting VAP in individual patients. These findings suggest that focusing exclusively on pathogen burden may not adequately inform VAP diagnosis.
AB - We sought to determine whether temporal changes in the lower airway microbiome are associated with ventilator-associated pneumonia (VAP) in children. Using a multicentre prospective study of children aged 31 days to 18 years requiring mechanical ventilation support for >72 h, daily tracheal aspirates were collected and analysed by sequencing of the 16S rRNA gene. VAP was assessed using 2008 Centers for Disease Control and Prevention paediatric criteria. The association between microbial factors and VAP was evaluated using joint longitudinal time-to-event modelling, matched case–control comparisons and unsupervised clustering. Out of 366 eligible subjects, 66 (15%) developed VAP at a median of 5 (interquartile range 3–5) days post intubation. At intubation, there was no difference in total bacterial load (TBL), but Shannon diversity and the relative abundance of Streptococcus, Lactobacillales and Prevotella were lower for VAP subjects versus non-VAP subjects. However, higher TBL on each sequential day was associated with a lower hazard (hazard ratio 0.39, 95% CI 0.23–0.64) for developing VAP, but sequential values of diversity were not associated with VAP. Similar findings were observed from the matched analysis and unsupervised clustering. The most common dominant VAP pathogens included Prevotella species (19%), Pseudomonas aeruginosa (14%) and Streptococcus mitis/pneumoniae (10%). Mycoplasma and Ureaplasma were also identified as dominant organisms in several subjects. In mechanically ventilated children, changes over time in microbial factors were marginally associated with VAP risk, although these changes were not suitable for predicting VAP in individual patients. These findings suggest that focusing exclusively on pathogen burden may not adequately inform VAP diagnosis.
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U2 - 10.1183/13993003.01829-2020
DO - 10.1183/13993003.01829-2020
M3 - Article
C2 - 33008935
AN - SCOPUS:85103226548
SN - 0903-1936
VL - 57
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 3
M1 - 2001829
ER -