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

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

doi:10.1016/S2666-5247(21)00327-X

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

Lancet Microbe. 2022 Apr;3(4):e294-e302. doi: 10.1016/S2666-5247(21)00327-X. Epub 2022 Mar 11.

Authors

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.

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.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents
Bacteria / genetics
Bacteria, Anaerobic / genetics
Bacteriology*
Coinfection*
Communicable Diseases*
Community-Acquired Infections*
High-Throughput Nucleotide Sequencing
Humans
Metagenomics
Pilot Projects
Pleural Diseases* / diagnosis
RNA, Ribosomal, 16S / genetics
Staphylococcus aureus / genetics

Substances

Anti-Bacterial Agents
RNA, Ribosomal, 16S

Abstract

Publication types

MeSH terms

Substances

Grants and funding