TY - JOUR
T1 - Lower respiratory tract infections in children requiring mechanical ventilation
T2 - a multicentre prospective surveillance study incorporating airway metagenomics
AU - Tsitsiklis, Alexandra
AU - Osborne, Christina M.
AU - Kamm, Jack
AU - Williamson, Kayla
AU - Kalantar, Katrina
AU - Dudas, Gytis
AU - Caldera, Saharai
AU - Lyden, Amy
AU - Tan, Michelle
AU - Neff, Norma
AU - Soesanto, Victoria
AU - Harris, J. Kirk
AU - Ambroggio, Lilliam
AU - Maddux, Aline B.
AU - Carpenter, Todd C.
AU - Reeder, Ron W.
AU - Locandro, Chris
AU - Simões, Eric A.F.
AU - Leroue, Matthew K.
AU - Hall, Mark W.
AU - Zuppa, Athena F.
AU - Carcillo, Joseph
AU - Meert, Kathleen L.
AU - Sapru, Anil
AU - Pollack, Murray M.
AU - McQuillen, Patrick S.
AU - Notterman, Daniel A.
AU - Dean, J. Michael
AU - Zinter, Matt S.
AU - Wagner, Brandie D.
AU - DeRisi, Joseph L.
AU - Mourani, Peter M.
AU - Langelier, Charles R.
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license
PY - 2022/4
Y1 - 2022/4
N2 - Background: 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. Methods: 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. Findings: 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. Interpretation: 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.
AB - Background: 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. Methods: 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. Findings: 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. Interpretation: 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.
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U2 - 10.1016/S2666-5247(21)00304-9
DO - 10.1016/S2666-5247(21)00304-9
M3 - Article
C2 - 35544065
AN - SCOPUS:85127165842
SN - 2666-5247
VL - 3
SP - e284-e293
JO - The Lancet Microbe
JF - The Lancet Microbe
IS - 4
ER -