Observational Study

. 2022 Apr;3(4):e294-e302.

doi: 10.1016/S2666-5247(21)00327-X. Epub 2022 Mar 11.

The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing

Nikolaos I Kanellakis¹, John M Wrightson², Stephen Gerry³, Nicholas Ilott⁴, John P Corcoran², Eihab O Bedawi², Rachelle Asciak⁵, Andrey Nezhentsev⁶, Anand Sundaralingam², Rob J Hallifax², Greta M Economides⁶, Lucy R Bland⁶, Elizabeth Daly⁶, Xuan Yao⁷, Nick A Maskell⁸, Robert F Miller⁹, Derrick W Crook¹⁰, Timothy S C Hinks¹¹, Tao Dong⁷, Ioannis Psallidas⁵, Najib M Rahman¹²

Affiliations

¹ Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences, China Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. Electronic address: nikolaos.kanellakis@ndm.ox.ac.uk.
² Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
³ Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
⁴ Oxford Centre for Microbiome Studies, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
⁵ Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁶ Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁷ Chinese Academy of Medical Sciences, China Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
⁸ Academic Respiratory Unit, University of Bristol Medical School Translational Health Sciences, Bristol, UK; North Bristol Lung Centre, North Bristol NHS Trust, Bristol, UK.
⁹ Institute for Global Health, University College London, London, UK.
¹⁰ Nuffield Department of Medicine, University of Oxford and John Radcliffe Hospital, Oxford, UK; National Institute of Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
¹¹ Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
¹² Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences, China Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.

PMID: 35544066
PMCID: PMC8967721
DOI: 10.1016/S2666-5247(21)00327-X

Observational Study

The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing

Nikolaos I Kanellakis et al. Lancet Microbe. 2022 Apr.

. 2022 Apr;3(4):e294-e302.

doi: 10.1016/S2666-5247(21)00327-X. Epub 2022 Mar 11.

Authors

Affiliations

¹ Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences, China Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. Electronic address: nikolaos.kanellakis@ndm.ox.ac.uk.
² Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
³ Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
⁴ Oxford Centre for Microbiome Studies, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
⁵ Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁶ Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁷ Chinese Academy of Medical Sciences, China Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
⁸ Academic Respiratory Unit, University of Bristol Medical School Translational Health Sciences, Bristol, UK; North Bristol Lung Centre, North Bristol NHS Trust, Bristol, UK.
⁹ Institute for Global Health, University College London, London, UK.
¹⁰ Nuffield Department of Medicine, University of Oxford and John Radcliffe Hospital, Oxford, UK; National Institute of Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
¹¹ Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
¹² Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences, China Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.

PMID: 35544066
PMCID: PMC8967721
DOI: 10.1016/S2666-5247(21)00327-X

Abstract

Background: 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.

Methods: 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.

Findings: 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).

Interpretation: 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.

Funding: 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.

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Conflict of interest statement

Declaration of interests IP works for AstraZeneca in a non-related field. TSCH reports grants from the Wellcome Trust and The Guardians of the Beit Fellowship, during the conduct of the study; personal fees from AstraZeneca, TEVA, and Peer Voice; grants from Pfizer, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, University of Oxford, Sensyne Health, and Kymab, outside the submitted work. RFM reports personal fees from Gilead, outside the submitted work. All other authors declare no competing interests.

Figures

**Figure 1**
Pleural infection is predominately a polymicrobial disease (A) The histograms show the counts of detected pathogens in each sample within each of the five groups, based on dominant pathogen abundance. (B) Heatmap of unsupervised hierarchical clustering using the Bray-Curtis distance and the complete-linkage method; the colour of the first column denotes the bacterial class of the most abundant pathogen in the sample; each row is a sample and each column is a pathogen group; the colour of each cell represents the abundance (proportion of bacterial reads) of each pathogen group in each sample; red represents high and dark blue low abundance.

**Figure 2**
Community-acquired and hospital-acquired pleural infections show distinct bacterial patterns Phylogeny trees of community-acquired (A) and hospital-acquired (B) pleural infections. The colours of the circles represent the pathogen class and the size represents their relative abundance. NA=not available.

**Figure 3**
Monomicrobial and polymicrobial community-acquired pleural infections exhibit diverse bacterial patterns Individual dots are joined by a line exclusively to aid readability. (A) Line plot showing the average abundance of each pathogen class per group for community-acquired pleural infections. (B) Line plot showing the frequency (%) of samples containing pathogens of each bacterial class per sample group. (C) Line plot presenting the frequency (%) of each bacterial class per sample group. NA=not available.

See this image and copyright information in PMC

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The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing

Affiliations

The bacteriology of pleural infection (TORPIDS): an exploratory metagenomics analysis through next generation sequencing

Authors

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Abstract

Conflict of interest statement

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