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

Nikolaos I Kanellakis, PhD; John M Wrightson, DPhil; Stephen Gerry, PhD; Nicholas Ilott, PhD; John P Corcoran, MRCP; Eihab O Bedawi, MRCP; Rachelle Asciak, MD; Andrey Nezhentsev, BA; Anand Sundaralingam, MRCP; Rob J Hallifax, DPhil; Greta M Economides, BA; Lucy R Bland, BA; Elizabeth Daly, BA; Xuan Yao, PhD; Nick A Maskell, ProfDM; Robert F Miller, ProfFRCP; Derrick W Crook, ProfFRCP; Timothy S C Hinks, PhD; Tao Dong, ProfDPhil; Ioannis Psallidas, PhD; Najib M Rahman, ProfDPhil

The Lancet Microbe (Apr 2022)

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

Nikolaos I Kanellakis, PhD,
John M Wrightson, DPhil,
Stephen Gerry, PhD,
Nicholas Ilott, PhD,
John P Corcoran, MRCP,
Eihab O Bedawi, MRCP,
Rachelle Asciak, MD,
Andrey Nezhentsev, BA,
Anand Sundaralingam, MRCP,
Rob J Hallifax, DPhil,
Greta M Economides, BA,
Lucy R Bland, BA,
Elizabeth Daly, BA,
Xuan Yao, PhD,
Nick A Maskell, ProfDM,
Robert F Miller, ProfFRCP,
Derrick W Crook, ProfFRCP,
Timothy S C Hinks, PhD,
Tao Dong, ProfDPhil,
Ioannis Psallidas, PhD,
Najib M Rahman, ProfDPhil

Affiliations

Nikolaos I Kanellakis, PhD: 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; Correspondence to: Dr Nikolaos I Kanellakis, Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK
John M Wrightson, DPhil: Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Stephen Gerry, PhD: Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
Nicholas Ilott, PhD: Oxford Centre for Microbiome Studies, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
John P Corcoran, MRCP: Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Eihab O Bedawi, MRCP: Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Rachelle Asciak, MD: 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
Andrey Nezhentsev, BA: Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Anand Sundaralingam, MRCP: Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Rob J Hallifax, DPhil: Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Greta M Economides, BA: Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Lucy R Bland, BA: Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Elizabeth Daly, BA: Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Xuan Yao, PhD: 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
Nick A Maskell, ProfDM: Academic Respiratory Unit, University of Bristol Medical School Translational Health Sciences, Bristol, UK; North Bristol Lung Centre, North Bristol NHS Trust, Bristol, UK
Robert F Miller, ProfFRCP: Institute for Global Health, University College London, London, UK
Derrick W Crook, ProfFRCP: 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
Timothy S C Hinks, PhD: 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
Tao Dong, ProfDPhil: 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
Ioannis Psallidas, PhD: 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
Najib M Rahman, ProfDPhil: 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

Journal volume & issue: Vol. 3, no. 4
pp. e294 – e302

Abstract

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Summary: 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.

Published in The Lancet Microbe

ISSN: 2666-5247 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General); Science: Microbiology
Website: https://www.journals.elsevier.com/the-lancet-microbe

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