Lower respiratory tract infections in children requiring mechanical ventilation: a multicentre prospective surveillance study incorporating airway metagenomics.

TitleLower respiratory tract infections in children requiring mechanical ventilation: a multicentre prospective surveillance study incorporating airway metagenomics.
Publication TypeJournal Article
Year of Publication2022
AuthorsTsitsiklis, A, Osborne, CM, Kamm, J, Williamson, K, Kalantar, K, Dudas, G, Caldera, S, Lyden, A, Tan, M, Neff, N, Soesanto, V, J Harris, K, Ambroggio, L, Maddux, AB, Carpenter, TC, Reeder, RW, Locandro, C, Simões, EAF, Leroue, MK, Hall, MW, Zuppa, AF, Carcillo, J, Meert, KL, Sapru, A, Pollack, MM, McQuillen, PS, Notterman, DA, J Dean, M, Zinter, MS, Wagner, BD, DeRisi, JL, Mourani, PM, Langelier, CR
JournalLancet Microbe
Volume3
Issue4
Paginatione284-e293
Date Published2022 Apr
ISSN2666-5247
KeywordsBacteria, Child, Cohort Studies, Critical Illness, Haemophilus influenzae, Humans, Metagenomics, Moraxella catarrhalis, Prospective Studies, Respiration, Artificial, Respiratory Syncytial Virus, Human, Respiratory Tract Infections, United States
Abstract

<p><b>BACKGROUND: </b>Lower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We combined traditional diagnostics with metagenomic next generation sequencing (mNGS) to evaluate the cause of LRTI in critically ill children.</p><p><b>METHODS: </b>We conducted a prospective, multicentre cohort study of critically ill children aged 31 days to 17 years with respiratory failure requiring mechanical ventilation (>72 h) in the USA. By combining bacterial culture and upper respiratory viral PCR testing with mNGS of tracheal aspirate collected from all patients within 24 h of intubation, we determined the prevalence, age distribution, and seasonal variation of viral and bacterial respiratory pathogens detected by either method in children with or without LRTI.</p><p><b>FINDINGS: </b>Between Feb 26, 2015, and Dec 31, 2017, of the 514 enrolled patients, 397 were eligible and included in the study (276 children with LRTI and 121 with no evidence of LRTI). A presumptive microbiological cause was identified in 255 (92%) children with LRTI, with respiratory syncytial virus (127 [46%]), Haemophilus influenzae (70 [25%]), and Moraxella catarrhalis (65 [24%]) being most prevalent. mNGS identified uncommon pathogens including Ureaplasma parvum and Bocavirus. Co-detection of viral and bacterial pathogens occurred in 144 (52%) patients. Incidental carriage of potentially pathogenic microbes occurred in 82 (68%) children without LRTI, with rhinovirus (30 [25%]) being most prevalent. Respiratory syncytial virus (p<0·0001), H influenzae (p=0·0006), and M catarrhalis (p=0·0002) were most common in children younger than 5 years. Viral and bacterial LRTI occurred predominantly during winter months.</p><p><b>INTERPRETATION: </b>These findings demonstrate that respiratory syncytial virus, H influenzae, and M catarrhalis contribute disproportionately to severe paediatric LRTI, co-infections are common, and incidental carriage of potentially pathogenic microbes occurs frequently. Further, we provide a framework for future epidemiological and emerging pathogen surveillance studies, highlighting the potential for metagenomics to enhance clinical diagnosis.</p><p><b>FUNDING: </b>US National Institutes of Health and CZ Biohub.</p>

DOI10.1016/S2666-5247(21)00304-9
Alternate JournalLancet Microbe
PubMed ID35544065
PubMed Central IDPMC9446282
Grant ListUG1 HD050096 / HD / NICHD NIH HHS / United States
UG1 HD063108 / HD / NICHD NIH HHS / United States
R01 HL155418 / HL / NHLBI NIH HHS / United States
K23 HL138461 / HL / NHLBI NIH HHS / United States
UG1 HD034116 / HD / NICHD NIH HHS / United States
U01 HD049934 / HD / NICHD NIH HHS / United States
UG1 HD049981 / HD / NICHD NIH HHS / United States
K23 HL146936 / HL / NHLBI NIH HHS / United States
UG1 HD049983 / HD / NICHD NIH HHS / United States
UG1 HD083170 / HD / NICHD NIH HHS / United States
UG1 HD083166 / HD / NICHD NIH HHS / United States
R01 HL124103 / HL / NHLBI NIH HHS / United States
UG1 HD083171 / HD / NICHD NIH HHS / United States