The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing
<strong>Background</strong> Pleural infection is a common and severe disease with high morbidity and mortality worldwide. The knowledge of pleural infection bacteriology remains incomplete, as pathogen detection methods based on culture have insufficient sensitivity and are biased to sel...
Main Authors: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
Elsevier
2022
|
_version_ | 1797106678571728896 |
---|---|
author | Kanellakis, NI Wrightson, JM Gerry, S Ilott, N Corcoran, JP Bedawi, EO Asciak, R Nezhentsev, A Sundaralingam, A Hallifax, RJ Economides, GM Bland, LR Daly, E Yao, X Maskell, NA Miller, RF Crook, DW Hinks, TSC Dong, T Psallidas, I Rahman, NM |
author_facet | Kanellakis, NI Wrightson, JM Gerry, S Ilott, N Corcoran, JP Bedawi, EO Asciak, R Nezhentsev, A Sundaralingam, A Hallifax, RJ Economides, GM Bland, LR Daly, E Yao, X Maskell, NA Miller, RF Crook, DW Hinks, TSC Dong, T Psallidas, I Rahman, NM |
author_sort | Kanellakis, NI |
collection | OXFORD |
description | <strong>Background</strong>
Pleural infection is a common and severe disease with high morbidity and mortality worldwide. The knowledge of pleural infection bacteriology remains incomplete, as pathogen detection methods based on culture have insufficient sensitivity and are biased to selected microbes. We designed a study with the aim to discover and investigate the total microbiome of pleural infection and assess the correlation between bacterial patterns and 1-year survival of patients.
<br>
<strong>Methods</strong>
We assessed 243 pleural fluid samples from the PILOT study, a prospective observational study on pleural infection, with 16S rRNA next generation sequencing. 20 pleural fluid samples from patients with pleural effusion due to a non-infectious cause and ten PCR-grade water samples were used as controls. Downstream analysis was done with the DADA2 pipeline. We applied multivariate Cox regression analyses to investigate the association between bacterial patterns and 1-year survival of patients with pleural infection.
<br>
<strong>Findings</strong>
Pleural infection was predominately polymicrobial (192 [79%] of 243 samples), with diverse bacterial frequencies observed in monomicrobial and polymicrobial disease and in both community-acquired and hospital-acquired infection. Mixed anaerobes and other Gram-negative bacteria predominated in community-acquired polymicrobial infection whereas Streptococcus pneumoniae prevailed in monomicrobial cases. The presence of anaerobes (hazard ratio 0·46, 95% CI 0·24–0·86, p=0·015) or bacteria of the Streptococcus anginosus group (0·43, 0·19–0·97, p=0·043) was associated with better patient survival, whereas the presence (5·80, 2·37–14·21, p<0·0001) or dominance (3·97, 1·20–13·08, p=0·024) of Staphylococcus aureus was linked with lower survival. Moreover, dominance of Enterobacteriaceae was associated with higher risk of death (2·26, 1·03–4·93, p=0·041).
<br>
<strong>Interpretation</strong>
Pleural infection is a predominantly polymicrobial infection, explaining the requirement for broad spectrum antibiotic cover in most individuals. High mortality infection associated with S aureus and Enterobacteriaceae favours more aggressive, with a narrower spectrum, antibiotic strategies.
<br>
<strong>Funding</strong>
UK Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, Wellcome Trust, Oxfordshire Health Services Research Committee, Chinese Academy of Medical Sciences, and John Fell Fund. |
first_indexed | 2024-03-07T07:04:30Z |
format | Journal article |
id | oxford-uuid:3f8d3672-d18f-451a-bf09-5c82f393f8ba |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T07:04:30Z |
publishDate | 2022 |
publisher | Elsevier |
record_format | dspace |
spelling | oxford-uuid:3f8d3672-d18f-451a-bf09-5c82f393f8ba2022-04-29T12:55:48ZThe bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3f8d3672-d18f-451a-bf09-5c82f393f8baEnglishSymplectic ElementsElsevier2022Kanellakis, NIWrightson, JMGerry, SIlott, NCorcoran, JPBedawi, EOAsciak, RNezhentsev, ASundaralingam, AHallifax, RJEconomides, GMBland, LRDaly, EYao, XMaskell, NAMiller, RFCrook, DWHinks, TSCDong, TPsallidas, IRahman, NM<strong>Background</strong> Pleural infection is a common and severe disease with high morbidity and mortality worldwide. The knowledge of pleural infection bacteriology remains incomplete, as pathogen detection methods based on culture have insufficient sensitivity and are biased to selected microbes. We designed a study with the aim to discover and investigate the total microbiome of pleural infection and assess the correlation between bacterial patterns and 1-year survival of patients. <br> <strong>Methods</strong> We assessed 243 pleural fluid samples from the PILOT study, a prospective observational study on pleural infection, with 16S rRNA next generation sequencing. 20 pleural fluid samples from patients with pleural effusion due to a non-infectious cause and ten PCR-grade water samples were used as controls. Downstream analysis was done with the DADA2 pipeline. We applied multivariate Cox regression analyses to investigate the association between bacterial patterns and 1-year survival of patients with pleural infection. <br> <strong>Findings</strong> Pleural infection was predominately polymicrobial (192 [79%] of 243 samples), with diverse bacterial frequencies observed in monomicrobial and polymicrobial disease and in both community-acquired and hospital-acquired infection. Mixed anaerobes and other Gram-negative bacteria predominated in community-acquired polymicrobial infection whereas Streptococcus pneumoniae prevailed in monomicrobial cases. The presence of anaerobes (hazard ratio 0·46, 95% CI 0·24–0·86, p=0·015) or bacteria of the Streptococcus anginosus group (0·43, 0·19–0·97, p=0·043) was associated with better patient survival, whereas the presence (5·80, 2·37–14·21, p<0·0001) or dominance (3·97, 1·20–13·08, p=0·024) of Staphylococcus aureus was linked with lower survival. Moreover, dominance of Enterobacteriaceae was associated with higher risk of death (2·26, 1·03–4·93, p=0·041). <br> <strong>Interpretation</strong> Pleural infection is a predominantly polymicrobial infection, explaining the requirement for broad spectrum antibiotic cover in most individuals. High mortality infection associated with S aureus and Enterobacteriaceae favours more aggressive, with a narrower spectrum, antibiotic strategies. <br> <strong>Funding</strong> UK Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, Wellcome Trust, Oxfordshire Health Services Research Committee, Chinese Academy of Medical Sciences, and John Fell Fund. |
spellingShingle | Kanellakis, NI Wrightson, JM Gerry, S Ilott, N Corcoran, JP Bedawi, EO Asciak, R Nezhentsev, A Sundaralingam, A Hallifax, RJ Economides, GM Bland, LR Daly, E Yao, X Maskell, NA Miller, RF Crook, DW Hinks, TSC Dong, T Psallidas, I Rahman, NM The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing |
title | The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing |
title_full | The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing |
title_fullStr | The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing |
title_full_unstemmed | The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing |
title_short | The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing |
title_sort | bacteriology of pleural infection torpids an exploratory metagenomics analysis through next generation sequencing |
work_keys_str_mv | AT kanellakisni thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT wrightsonjm thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT gerrys thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT ilottn thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT corcoranjp thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT bedawieo thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT asciakr thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT nezhentseva thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT sundaralingama thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT hallifaxrj thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT economidesgm thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT blandlr thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT dalye thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT yaox thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT maskellna thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT millerrf thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT crookdw thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT hinkstsc thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT dongt thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT psallidasi thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT rahmannm thebacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT kanellakisni bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT wrightsonjm bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT gerrys bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT ilottn bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT corcoranjp bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT bedawieo bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT asciakr bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT nezhentseva bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT sundaralingama bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT hallifaxrj bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT economidesgm bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT blandlr bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT dalye bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT yaox bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT maskellna bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT millerrf bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT crookdw bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT hinkstsc bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT dongt bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT psallidasi bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing AT rahmannm bacteriologyofpleuralinfectiontorpidsanexploratorymetagenomicsanalysisthroughnextgenerationsequencing |