TY - JOUR T1 - Temporal airway microbiome changes related to ventilator associated pneumonia in children JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01829-2020 SP - 2001829 AU - Peter M. Mourani AU - Marci K. Sontag AU - Kayla M. Williamson AU - J. Kirk Harris AU - Ron Reeder AU - Chris Locandro AU - Todd C. Carpenter AU - Aline B. Maddux AU - Katherine Ziegler AU - Eric A.F. Simões AU - Christina M. Osborne AU - Lilliam Ambroggio AU - Matthew K. Leroue AU - Charles E. Robertson AU - Charles Langelier AU - Joseph L. DeRisi AU - Jack Kamm AU - Mark W. Hall AU - Athena F. Zuppa AU - Joseph Carcillo AU - Kathleen Meert AU - Anil Sapru AU - Murray M. Pollack AU - Patrick McQuillen AU - Daniel A. Notterman AU - J. Michael Dean AU - Brandie D. Wagner AU - Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) Y1 - 2020/01/01 UR - http://erj.ersjournals.com/content/early/2020/09/09/13993003.01829-2020.abstract N2 - We sought to determine whether temporal changes in the lower airway microbiome are associated with ventilator-associated pneumonia (VAP) in children.Using a multicenter prospective study of children 31 days to 18 years requiring mechanical ventilation (MV) support for >72 h, daily tracheal aspirates were collected and analysed by sequencing of the 16S rRNA gene. VAP was assessed using 2008 CDC pediatric criteria. The association between microbial factors and VAP was evaluated using joint longitudinal time-to-event modelling, matched case-control comparisons, and unsupervised clustering.Of 366 eligible subjects, 66 (15%) developed VAP at a median of 5 (IQR: 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 (HR: 0.39; 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Mourani reports grants from NIH NHLBI, grants from NIH NICHD, during the conduct of the study.Conflict of interest: Dr. Sontag reports grants from NIH NHLBI, during the conduct of the study.Conflict of interest: Ms. Williamson has nothing to disclose.Conflict of interest: Dr. Harris has nothing to disclose.Conflict of interest: Dr. Reeder has nothing to disclose.Conflict of interest: Dr. Locandro has nothing to disclose.Conflict of interest: Dr. Carpenter reports grants from NIH NHLBI, grants from NIH NICHD, during the conduct of the study.Conflict of interest: Dr. Maddux reports a grant from Parker B. Francis Foundation (Fellowship Award) and a grant from NIH/NICHD K23HD096018, outside the submitted work.Conflict of interest: K. Ziegler reports grants from NIH NHLBI during the conduct of the study.Conflict of interest: Dr. Simoes reports grants from NIH NHLBI, during the conduct of the study.Conflict of interest: Dr. Osborne has nothing to disclose.Conflict of interest: Dr. Ambroggio has nothing to disclose.Conflict of interest: Dr. Leroue has nothing to disclose.Conflict of interest: Dr. Robertson has nothing to disclose.Conflict of interest: Dr. Langelier has nothing to disclose.Conflict of interest: Dr. DeRisi reports grants from NIH NHLBI, during the conduct of the study.Conflict of interest: Dr. Kamm has nothing to disclose.Conflict of interest: Dr. Hall reports grants from NIH NICHD, during the conduct of the study.Conflict of interest: Dr. Zuppa has nothing to disclose.Conflict of interest: Dr. Carcillo has nothing to disclose.Conflict of interest: Dr. Meert reports grants from NIH, during the conduct of the study.Conflict of interest: Dr. Sapru reports grants from NIH NICHD, during the conduct of the study.Conflict of interest: Dr. Pollack reports grants from NIH, during the conduct of the study.Conflict of interest: Dr. McQuillen reports grants from NIH NICHD, during the conduct of the study.Conflict of interest: Dr. Notterman has nothing to disclose.Conflict of interest: Dr. Dean reports grants from NIH, during the conduct of the study.Conflict of interest: Dr. Wagner reports grants from NIH NHLBI, during the conduct of the study. 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