The rapid detection of respiratory pathogens in critically ill children

John A. Clark; Andrew Conway Morris; Martin D. Curran; Deborah White; Esther Daubney; Iain R.L. Kean; Vilas Navapurkar; Josefin Bartholdson Scott; Mailis Maes; Rachel Bousfield; M. Estée Török; David Inwald; Zhenguang Zhang; Shruti Agrawal; Constantinos Kanaris; Fahad Khokhar; Theodore Gouliouris; Stephen Baker; Nazima Pathan

doi:10.1186/s13054-023-04303-1

The rapid detection of respiratory pathogens in critically ill children

John A. Clark^*, Andrew Conway Morris, Martin D. Curran, Deborah White, Esther Daubney, Iain R.L. Kean, Vilas Navapurkar, Josefin Bartholdson Scott, Mailis Maes, Rachel Bousfield, M. Estée Török, David Inwald, Zhenguang Zhang, Shruti Agrawal, Constantinos Kanaris, Fahad Khokhar, Theodore Gouliouris, Stephen Baker, Nazima Pathan

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Purpose: Respiratory infections are the most common reason for admission to paediatric intensive care units (PICU). Most patients with lower respiratory tract infection (LRTI) receive broad-spectrum antimicrobials, despite low rates of bacterial culture confirmation. Here, we evaluated a molecular diagnostic test for LRTI to inform the better use of antimicrobials. Methods: The Rapid Assay for Sick Children with Acute Lung infection Study was a single-centre, prospective, observational cohort study of mechanically ventilated children (> 37/40 weeks corrected gestation to 18 years) with suspected community acquired or ventilator-associated LRTI. We evaluated the use of a 52-pathogen custom TaqMan Array Card (TAC) to identify pathogens in non-bronchoscopic bronchoalveolar lavage (mini-BAL) samples. TAC results were compared to routine microbiology testing. Primary study outcomes were sensitivity and specificity of TAC, and time to result. Results: We enrolled 100 patients, all of whom were tested with TAC and 91 of whom had matching culture samples. TAC had a sensitivity of 89.5% (95% confidence interval (CI₉₅) 66.9–98.7) and specificity of 97.9% (CI₉₅ 97.2–98.5) compared to routine bacterial and fungal culture. TAC took a median 25.8 h (IQR 9.1–29.8 h) from sample collection to result. Culture was significantly slower: median 110.4 h (IQR 85.2–141.6 h) for a positive result and median 69.4 h (IQR 52.8–78.6) for a negative result. Conclusions: TAC is a reliable and rapid adjunct diagnostic approach for LRTI in critically ill children, with the potential to aid early rationalisation of antimicrobial therapy.

Original language	English
Article number	11
Journal	Critical Care
Volume	27
Issue number	1
DOIs	https://doi.org/10.1186/s13054-023-04303-1
Publication status	Published - Dec 2023

Bibliographical note

Funding Information:
This project is funded by the Addenbrooke’s Charitable Trust, Cambridge University Hospitals (900240) (JAC, NP, MET, IRLK and SB) which provided funding for consumables and 16S rRNA gene sequencing of samples, in addition to the NIHR Cambridge Biomedical Research Centre. The authors also receive support from the Gates Cambridge Trust (OPP1144) (JAC); the Academy of Medical Sciences and the Health Foundation Clinician Scientist Fellowship (MET); Wellcome Trust (215515) (SB); Wellcome Trust Clinical Research Career Development Fellowship (WT 2055214/Z/16/Z) (ACM) MRC Clinician Scientist Fellowship (MR/V006118/1) (ACM); and Action Medical Research (NP, SB, MET) (GN2751, GN2903).This work was supported, in whole or in part, by the Bill & Melinda Gates Foundation (OPP1144). Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.

Funding Information:
The study was sponsored by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. Approval was granted by the Yorkshire and Humber-Bradford Leeds Research Ethics Committee (REC ref 20/YH/0089 on 26 March 2020). The trial was registered prior to commencement on ClinicalTrials.gov (NCT04233268).

Publisher Copyright:
© 2023, The Author(s).

Keywords

Critical care
Diagnostic techniques
Healthcare-associated pneumonia
Paediatric
Pneumonia
Respiratory system

Access to Document

10.1186/s13054-023-04303-1

Cite this

Clark, J. A., Conway Morris, A., Curran, M. D., White, D., Daubney, E., Kean, I. R. L., Navapurkar, V., Bartholdson Scott, J., Maes, M., Bousfield, R., Török, M. E., Inwald, D., Zhang, Z., Agrawal, S., Kanaris, C., Khokhar, F., Gouliouris, T., Baker, S., & Pathan, N. (2023). The rapid detection of respiratory pathogens in critically ill children. Critical Care, 27(1), Article 11. https://doi.org/10.1186/s13054-023-04303-1

@article{3462aaf4b1454667930799010aa8b2cf,

title = "The rapid detection of respiratory pathogens in critically ill children",

abstract = "Purpose: Respiratory infections are the most common reason for admission to paediatric intensive care units (PICU). Most patients with lower respiratory tract infection (LRTI) receive broad-spectrum antimicrobials, despite low rates of bacterial culture confirmation. Here, we evaluated a molecular diagnostic test for LRTI to inform the better use of antimicrobials. Methods: The Rapid Assay for Sick Children with Acute Lung infection Study was a single-centre, prospective, observational cohort study of mechanically ventilated children (> 37/40 weeks corrected gestation to 18 years) with suspected community acquired or ventilator-associated LRTI. We evaluated the use of a 52-pathogen custom TaqMan Array Card (TAC) to identify pathogens in non-bronchoscopic bronchoalveolar lavage (mini-BAL) samples. TAC results were compared to routine microbiology testing. Primary study outcomes were sensitivity and specificity of TAC, and time to result. Results: We enrolled 100 patients, all of whom were tested with TAC and 91 of whom had matching culture samples. TAC had a sensitivity of 89.5% (95% confidence interval (CI95) 66.9–98.7) and specificity of 97.9% (CI95 97.2–98.5) compared to routine bacterial and fungal culture. TAC took a median 25.8 h (IQR 9.1–29.8 h) from sample collection to result. Culture was significantly slower: median 110.4 h (IQR 85.2–141.6 h) for a positive result and median 69.4 h (IQR 52.8–78.6) for a negative result. Conclusions: TAC is a reliable and rapid adjunct diagnostic approach for LRTI in critically ill children, with the potential to aid early rationalisation of antimicrobial therapy.",

keywords = "Critical care, Diagnostic techniques, Healthcare-associated pneumonia, Paediatric, Pneumonia, Respiratory system",

author = "Clark, {John A.} and {Conway Morris}, Andrew and Curran, {Martin D.} and Deborah White and Esther Daubney and Kean, {Iain R.L.} and Vilas Navapurkar and {Bartholdson Scott}, Josefin and Mailis Maes and Rachel Bousfield and T{\"o}r{\"o}k, {M. Est{\'e}e} and David Inwald and Zhenguang Zhang and Shruti Agrawal and Constantinos Kanaris and Fahad Khokhar and Theodore Gouliouris and Stephen Baker and Nazima Pathan",

note = "Funding Information: This project is funded by the Addenbrooke{\textquoteright}s Charitable Trust, Cambridge University Hospitals (900240) (JAC, NP, MET, IRLK and SB) which provided funding for consumables and 16S rRNA gene sequencing of samples, in addition to the NIHR Cambridge Biomedical Research Centre. The authors also receive support from the Gates Cambridge Trust (OPP1144) (JAC); the Academy of Medical Sciences and the Health Foundation Clinician Scientist Fellowship (MET); Wellcome Trust (215515) (SB); Wellcome Trust Clinical Research Career Development Fellowship (WT 2055214/Z/16/Z) (ACM) MRC Clinician Scientist Fellowship (MR/V006118/1) (ACM); and Action Medical Research (NP, SB, MET) (GN2751, GN2903).This work was supported, in whole or in part, by the Bill & Melinda Gates Foundation (OPP1144). Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. Funding Information: The study was sponsored by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. Approval was granted by the Yorkshire and Humber-Bradford Leeds Research Ethics Committee (REC ref 20/YH/0089 on 26 March 2020). The trial was registered prior to commencement on ClinicalTrials.gov (NCT04233268). Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1186/s13054-023-04303-1",

language = "English",

volume = "27",

journal = "Critical Care",

issn = "1364-8535",

publisher = "BioMed Central Ltd.",

number = "1",

}

Clark, JA, Conway Morris, A, Curran, MD, White, D, Daubney, E, Kean, IRL, Navapurkar, V, Bartholdson Scott, J, Maes, M, Bousfield, R, Török, ME, Inwald, D, Zhang, Z, Agrawal, S, Kanaris, C, Khokhar, F, Gouliouris, T, Baker, S & Pathan, N 2023, 'The rapid detection of respiratory pathogens in critically ill children', Critical Care, vol. 27, no. 1, 11. https://doi.org/10.1186/s13054-023-04303-1

TY - JOUR

T1 - The rapid detection of respiratory pathogens in critically ill children

AU - Clark, John A.

AU - Conway Morris, Andrew

AU - Curran, Martin D.

AU - White, Deborah

AU - Daubney, Esther

AU - Kean, Iain R.L.

AU - Navapurkar, Vilas

AU - Bartholdson Scott, Josefin

AU - Maes, Mailis

AU - Bousfield, Rachel

AU - Török, M. Estée

AU - Inwald, David

AU - Zhang, Zhenguang

AU - Agrawal, Shruti

AU - Kanaris, Constantinos

AU - Khokhar, Fahad

AU - Gouliouris, Theodore

AU - Baker, Stephen

AU - Pathan, Nazima

N1 - Funding Information: This project is funded by the Addenbrooke’s Charitable Trust, Cambridge University Hospitals (900240) (JAC, NP, MET, IRLK and SB) which provided funding for consumables and 16S rRNA gene sequencing of samples, in addition to the NIHR Cambridge Biomedical Research Centre. The authors also receive support from the Gates Cambridge Trust (OPP1144) (JAC); the Academy of Medical Sciences and the Health Foundation Clinician Scientist Fellowship (MET); Wellcome Trust (215515) (SB); Wellcome Trust Clinical Research Career Development Fellowship (WT 2055214/Z/16/Z) (ACM) MRC Clinician Scientist Fellowship (MR/V006118/1) (ACM); and Action Medical Research (NP, SB, MET) (GN2751, GN2903).This work was supported, in whole or in part, by the Bill & Melinda Gates Foundation (OPP1144). Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. Funding Information: The study was sponsored by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. Approval was granted by the Yorkshire and Humber-Bradford Leeds Research Ethics Committee (REC ref 20/YH/0089 on 26 March 2020). The trial was registered prior to commencement on ClinicalTrials.gov (NCT04233268). Publisher Copyright: © 2023, The Author(s).

PY - 2023/12

Y1 - 2023/12

N2 - Purpose: Respiratory infections are the most common reason for admission to paediatric intensive care units (PICU). Most patients with lower respiratory tract infection (LRTI) receive broad-spectrum antimicrobials, despite low rates of bacterial culture confirmation. Here, we evaluated a molecular diagnostic test for LRTI to inform the better use of antimicrobials. Methods: The Rapid Assay for Sick Children with Acute Lung infection Study was a single-centre, prospective, observational cohort study of mechanically ventilated children (> 37/40 weeks corrected gestation to 18 years) with suspected community acquired or ventilator-associated LRTI. We evaluated the use of a 52-pathogen custom TaqMan Array Card (TAC) to identify pathogens in non-bronchoscopic bronchoalveolar lavage (mini-BAL) samples. TAC results were compared to routine microbiology testing. Primary study outcomes were sensitivity and specificity of TAC, and time to result. Results: We enrolled 100 patients, all of whom were tested with TAC and 91 of whom had matching culture samples. TAC had a sensitivity of 89.5% (95% confidence interval (CI95) 66.9–98.7) and specificity of 97.9% (CI95 97.2–98.5) compared to routine bacterial and fungal culture. TAC took a median 25.8 h (IQR 9.1–29.8 h) from sample collection to result. Culture was significantly slower: median 110.4 h (IQR 85.2–141.6 h) for a positive result and median 69.4 h (IQR 52.8–78.6) for a negative result. Conclusions: TAC is a reliable and rapid adjunct diagnostic approach for LRTI in critically ill children, with the potential to aid early rationalisation of antimicrobial therapy.

AB - Purpose: Respiratory infections are the most common reason for admission to paediatric intensive care units (PICU). Most patients with lower respiratory tract infection (LRTI) receive broad-spectrum antimicrobials, despite low rates of bacterial culture confirmation. Here, we evaluated a molecular diagnostic test for LRTI to inform the better use of antimicrobials. Methods: The Rapid Assay for Sick Children with Acute Lung infection Study was a single-centre, prospective, observational cohort study of mechanically ventilated children (> 37/40 weeks corrected gestation to 18 years) with suspected community acquired or ventilator-associated LRTI. We evaluated the use of a 52-pathogen custom TaqMan Array Card (TAC) to identify pathogens in non-bronchoscopic bronchoalveolar lavage (mini-BAL) samples. TAC results were compared to routine microbiology testing. Primary study outcomes were sensitivity and specificity of TAC, and time to result. Results: We enrolled 100 patients, all of whom were tested with TAC and 91 of whom had matching culture samples. TAC had a sensitivity of 89.5% (95% confidence interval (CI95) 66.9–98.7) and specificity of 97.9% (CI95 97.2–98.5) compared to routine bacterial and fungal culture. TAC took a median 25.8 h (IQR 9.1–29.8 h) from sample collection to result. Culture was significantly slower: median 110.4 h (IQR 85.2–141.6 h) for a positive result and median 69.4 h (IQR 52.8–78.6) for a negative result. Conclusions: TAC is a reliable and rapid adjunct diagnostic approach for LRTI in critically ill children, with the potential to aid early rationalisation of antimicrobial therapy.

KW - Critical care

KW - Diagnostic techniques

KW - Healthcare-associated pneumonia

KW - Paediatric

KW - Pneumonia

KW - Respiratory system

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U2 - 10.1186/s13054-023-04303-1

DO - 10.1186/s13054-023-04303-1

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AN - SCOPUS:85146106042

SN - 1364-8535

VL - 27

JO - Critical Care

JF - Critical Care

IS - 1

M1 - 11

ER -

The rapid detection of respiratory pathogens in critically ill children

Abstract

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Keywords

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