Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units

Abstract Background Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secon...

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Autores principales:	Themoula Charalampous, Adela Alcolea-Medina, Luke B. Snell, Tom G. S. Williams, Rahul Batra, Christopher Alder, Andrea Telatin, Luigi Camporota, Christopher I. S. Meadows, Duncan Wyncoll, Nicholas A. Barrett, Carolyn J. Hemsley, Lisa Bryan, William Newsholme, Sara E. Boyd, Anna Green, Ula Mahadeva, Amita Patel, Penelope R. Cliff, Andrew J. Page, Justin O’Grady, Jonathan D. Edgeworth
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/3c7a335029394a13877c2e9c82267e9d
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spelling	oai:doaj.org-article:3c7a335029394a13877c2e9c82267e9d2021-11-21T12:27:14ZEvaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units10.1186/s13073-021-00991-y1756-994Xhttps://doaj.org/article/3c7a335029394a13877c2e9c82267e9d2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13073-021-00991-yhttps://doaj.org/toc/1756-994XAbstract Background Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secondary infection and nosocomial transmission of multi-drug-resistant (MDR) pathogens linked with the expansion of critical care capacity. Methods CMg using nanopore sequencing was evaluated in a proof-of-concept study on 43 respiratory samples from 34 intubated patients across seven intensive care units (ICUs) over a 9-week period during the first COVID-19 pandemic wave. Results An 8-h CMg workflow was 92% sensitive (95% CI, 75–99%) and 82% specific (95% CI, 57–96%) for bacterial identification based on culture-positive and culture-negative samples, respectively. CMg sequencing reported the presence or absence of β-lactam-resistant genes carried by Enterobacterales that would modify the initial guideline-recommended antibiotics in every case. CMg was also 100% concordant with quantitative PCR for detecting Aspergillus fumigatus from 4 positive and 39 negative samples. Molecular typing using 24-h sequencing data identified an MDR-K. pneumoniae ST307 outbreak involving 4 patients and an MDR-C. striatum outbreak involving 14 patients across three ICUs. Conclusion CMg testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance. The provision of this technology in a service setting could fundamentally change the multi-disciplinary team approach to managing ICU infections. The potential to improve the initial targeted treatment and rapidly detect unsuspected outbreaks of MDR-pathogens justifies further expedited clinical assessment of CMg.Themoula CharalampousAdela Alcolea-MedinaLuke B. SnellTom G. S. WilliamsRahul BatraChristopher AlderAndrea TelatinLuigi CamporotaChristopher I. S. MeadowsDuncan WyncollNicholas A. BarrettCarolyn J. HemsleyLisa BryanWilliam NewsholmeSara E. BoydAnna GreenUla MahadevaAmita PatelPenelope R. CliffAndrew J. PageJustin O’GradyJonathan D. EdgeworthBMCarticleMedicineRGeneticsQH426-470ENGenome Medicine, Vol 13, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Themoula Charalampous Adela Alcolea-Medina Luke B. Snell Tom G. S. Williams Rahul Batra Christopher Alder Andrea Telatin Luigi Camporota Christopher I. S. Meadows Duncan Wyncoll Nicholas A. Barrett Carolyn J. Hemsley Lisa Bryan William Newsholme Sara E. Boyd Anna Green Ula Mahadeva Amita Patel Penelope R. Cliff Andrew J. Page Justin O’Grady Jonathan D. Edgeworth Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units
description	Abstract Background Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secondary infection and nosocomial transmission of multi-drug-resistant (MDR) pathogens linked with the expansion of critical care capacity. Methods CMg using nanopore sequencing was evaluated in a proof-of-concept study on 43 respiratory samples from 34 intubated patients across seven intensive care units (ICUs) over a 9-week period during the first COVID-19 pandemic wave. Results An 8-h CMg workflow was 92% sensitive (95% CI, 75–99%) and 82% specific (95% CI, 57–96%) for bacterial identification based on culture-positive and culture-negative samples, respectively. CMg sequencing reported the presence or absence of β-lactam-resistant genes carried by Enterobacterales that would modify the initial guideline-recommended antibiotics in every case. CMg was also 100% concordant with quantitative PCR for detecting Aspergillus fumigatus from 4 positive and 39 negative samples. Molecular typing using 24-h sequencing data identified an MDR-K. pneumoniae ST307 outbreak involving 4 patients and an MDR-C. striatum outbreak involving 14 patients across three ICUs. Conclusion CMg testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance. The provision of this technology in a service setting could fundamentally change the multi-disciplinary team approach to managing ICU infections. The potential to improve the initial targeted treatment and rapidly detect unsuspected outbreaks of MDR-pathogens justifies further expedited clinical assessment of CMg.
format	article
author	Themoula Charalampous Adela Alcolea-Medina Luke B. Snell Tom G. S. Williams Rahul Batra Christopher Alder Andrea Telatin Luigi Camporota Christopher I. S. Meadows Duncan Wyncoll Nicholas A. Barrett Carolyn J. Hemsley Lisa Bryan William Newsholme Sara E. Boyd Anna Green Ula Mahadeva Amita Patel Penelope R. Cliff Andrew J. Page Justin O’Grady Jonathan D. Edgeworth
author_facet	Themoula Charalampous Adela Alcolea-Medina Luke B. Snell Tom G. S. Williams Rahul Batra Christopher Alder Andrea Telatin Luigi Camporota Christopher I. S. Meadows Duncan Wyncoll Nicholas A. Barrett Carolyn J. Hemsley Lisa Bryan William Newsholme Sara E. Boyd Anna Green Ula Mahadeva Amita Patel Penelope R. Cliff Andrew J. Page Justin O’Grady Jonathan D. Edgeworth
author_sort	Themoula Charalampous
title	Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units
title_short	Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units
title_full	Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units
title_fullStr	Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units
title_full_unstemmed	Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units
title_sort	evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded covid-19 intensive care units
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3c7a335029394a13877c2e9c82267e9d
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Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units

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