Abstract
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.
Abstract
In mechanically ventilated children, microbial factors were subtly different at intubation between those who did and did not develop VAP, and changes over time were marginally associated with VAP risk, suggesting other factors may contribute to VAP https://bit.ly/3ijsaTO
Footnotes
This article has supplementary material available from erj.ersjournals.com
The Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) members are as follows: Children's Hospital of Michigan: Kathleen L. Meert, Sabrina M. Heidemann; Children's Hospital of Philadelphia: Robert A. Berg, Athena F. Zuppa; Children's National Medical Center: Murray M. Pollack, Michael Bell, David L. Wessel, John T. Berger, Randall Burd; Children's Hospital Colorado: Peter M. Mourani, Todd C. Carpenter; Nationwide Children's Hospital: Mark W. Hall, Andrew R. Yates; Mattel Children's Hospital: Anil Sapru; Benioff Children's Hospital: Patrick McQuillen; Children's Hospital of Pittsburgh: Joseph A. Carcillo, Ericka L. Fink; University of Utah School of Medicine Data Coordinating Center: J. Michael Dean, Richard Holubkov, Katherine Sward, Ron W. Reeder, John VanBuren; Princeton University: Daniel A. Notterman.
Conflict of interest: P.M. Mourani reports grants from NIH NHLBI and NIH NICHD, during the conduct of the study.
Conflict of interest: M.K. Sontag reports grants from NIH NHLBI, during the conduct of the study.
Conflict of interest: K.M. Williamson has nothing to disclose.
Conflict of interest: J.K. Harris has nothing to disclose.
Conflict of interest: R. Reeder has nothing to disclose.
Conflict of interest: C. Locandro has nothing to disclose.
Conflict of interest: T.C. Carpenter reports grants from NIH NHLBI and NIH NICHD, during the conduct of the study.
Conflict of interest: A.B. Maddux reports a grant from Parker B. Francis Foundation (Fellowship Award) and 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: E.A.F. Simões reports grants from NIH NHLBI, during the conduct of the study.
Conflict of interest: C.M. Osborne has nothing to disclose.
Conflict of interest: L. Ambroggio has nothing to disclose.
Conflict of interest: M.K. Leroue has nothing to disclose.
Conflict of interest: C.E. Robertson has nothing to disclose.
Conflict of interest: C. Langelier has nothing to disclose.
Conflict of interest: J.L. DeRisi reports grants from NIH NHLBI, during the conduct of the study.
Conflict of interest: J. Kamm has nothing to disclose.
Conflict of interest: M.W. Hall reports grants from NIH NICHD, during the conduct of the study.
Conflict of interest: A.F. Zuppa has nothing to disclose.
Conflict of interest: J. Carcillo has nothing to disclose.
Conflict of interest: K. Meert reports grants from NIH, during the conduct of the study.
Conflict of interest: A. Sapru reports grants from NIH NICHD, during the conduct of the study.
Conflict of interest: M.M. Pollack reports grants from NIH, during the conduct of the study.
Conflict of interest: P. McQuillen reports grants from NIH NICHD, during the conduct of the study.
Conflict of interest: D.A. Notterman has nothing to disclose.
Conflict of interest: J.M. Dean reports grants from NIH, during the conduct of the study.
Conflict of interest: B.D. Wagner reports grants from NIH NHLBI, during the conduct of the study.
Support Statement: Supported in part, by the following cooperative agreements from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and Heart Lung Blood Institute (NHLBI), National Institutes of Health (NIH): UG1HD083171 (P.M. Mourani), 1R01HL124103 (P.M. Mourani and M.K. Sontag) UG1HD049983 (J. Carcillo), UG01HD049934 (R. Reeder, C. Locandro and J.M. Dean), UG1HD083170 (M.W. Hall), UG1HD050096 (K. Meert), UG1HD63108 (A.F. Zuppa), UG1HD083116 (A. Sapru), UG1HD083166 (P. McQuillen), UG1HD049981 (M.M. Pollack), and K23HL138461-01A1 (C. Langelier). The study sponsors were not involved in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the report for publication. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received May 18, 2020.
- Accepted September 2, 2020.
- Copyright ©ERS 2021
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