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Blood leukocyte transcriptomes in Gram-positive and Gram-negative community-acquired pneumonia

Liza Pereverzeva, Fabrice Uhel, Hessel Peters Sengers, Joe Butler, Lonneke A. van Vught, Katie L. Burnham, Emma E. Davenport, Julian C. Knight, Olaf L. Cremer, Marcus J. Schultz, Marc M.J. Bonten, Brendon P. Scicluna, Tom van der Poll on behalf of the MARS consortium
European Respiratory Journal 2022 59: 2101856; DOI: 10.1183/13993003.01856-2021
Liza Pereverzeva
1Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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  • ORCID record for Liza Pereverzeva
  • For correspondence: e.pereverzeva@amsterdamumc.nl
Fabrice Uhel
1Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Hessel Peters Sengers
1Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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  • ORCID record for Hessel Peters Sengers
Joe Butler
1Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Lonneke A. van Vught
1Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Katie L. Burnham
2Wellcome Sanger Institute, Cambridge, UK
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Emma E. Davenport
2Wellcome Sanger Institute, Cambridge, UK
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Julian C. Knight
3Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
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Olaf L. Cremer
4Dept of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
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Marcus J. Schultz
5Dept of Intensive Care, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
6Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand
7Nuffield Dept of Medicine, University of Oxford, Oxford, UK
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Marc M.J. Bonten
8Dept of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands
9Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
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Brendon P. Scicluna
1Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
10Dept of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Tom van der Poll
1Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
11Division of Infectious Diseases, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Abstract

Background Gram-positive and Gram-negative bacteria are the most common causative pathogens in community-acquired pneumonia (CAP) on the intensive care unit (ICU). The aim of this study was to determine whether the host immune response differs between Gram-positive and Gram-negative CAP upon ICU admission.

Methods 16 host response biomarkers providing insight into pathophysiological mechanisms implicated in sepsis and blood leukocyte transcriptomes were analysed in patients with CAP upon ICU admission in two tertiary hospitals in the Netherlands.

Results 309 patients with CAP with a definite or probable likelihood (determined by predefined criteria) were included. A causative pathogen was determined in 74.4% of admissions. Patients admitted with Gram-positive CAP (n=90) were not different from those admitted with Gram-negative CAP (n=75) regarding demographics, chronic comorbidities, severity of disease and mortality. Host response biomarkers reflective of systemic inflammation, coagulation activation and endothelial cell function, as well as blood leukocyte transcriptomes, were largely similar between Gram-positive and Gram-negative CAP. Blood leukocyte transcriptomes were also similar in Gram-positive and Gram-negative CAP in two independent validation cohorts. On a pathogen-specific level, Streptococcus pneumoniae and Escherichia coli induced the most distinct host immune response.

Conclusion Outcome and host response are similar in critically ill patients with CAP due to Gram-positive bacteria compared with Gram-negative bacteria.

Abstract

Outcome and host response in critically ill patients with community-acquired pneumonia are similar when caused by Gram-positive compared with Gram-negative bacteria https://bit.ly/3rMll2r

Footnotes

  • Conflict of interest: L. Pereverzeva has nothing to disclose.

  • Conflict of interest: F. Uhel has nothing to disclose.

  • Conflict of interest: H. Peters Sengers reports grants from the Dutch Kidney Foundation (Nierstichting) (grant 19OK009), outside the submitted work.

  • Conflict of interest: J. Butler has nothing to disclose.

  • Conflict of interest: L.A. van Vught has nothing to disclose.

  • Conflict of interest: K.L. Burnham has nothing to disclose.

  • Conflict of interest: E.E. Davenport has nothing to disclose.

  • Conflict of interest: J.C. Knight has nothing to disclose.

  • Conflict of interest: O.L. Cremer has nothing to disclose.

  • Conflict of interest: M.J. Schultz has nothing to disclose.

  • Conflict of interest: M.M.J. Bonten has nothing to disclose.

  • Conflict of interest: B.P. Scicluna has nothing to disclose.

  • Conflict of interest: T. van der Poll has nothing to disclose.

  • Support statement: This work was supported by the Center for Translational Molecular Medicine (04I-201). Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received October 27, 2020.
  • Accepted July 21, 2021.
  • Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
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Blood leukocyte transcriptomes in Gram-positive and Gram-negative community-acquired pneumonia
Liza Pereverzeva, Fabrice Uhel, Hessel Peters Sengers, Joe Butler, Lonneke A. van Vught, Katie L. Burnham, Emma E. Davenport, Julian C. Knight, Olaf L. Cremer, Marcus J. Schultz, Marc M.J. Bonten, Brendon P. Scicluna, Tom van der Poll
European Respiratory Journal Mar 2022, 59 (3) 2101856; DOI: 10.1183/13993003.01856-2021

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Blood leukocyte transcriptomes in Gram-positive and Gram-negative community-acquired pneumonia
Liza Pereverzeva, Fabrice Uhel, Hessel Peters Sengers, Joe Butler, Lonneke A. van Vught, Katie L. Burnham, Emma E. Davenport, Julian C. Knight, Olaf L. Cremer, Marcus J. Schultz, Marc M.J. Bonten, Brendon P. Scicluna, Tom van der Poll
European Respiratory Journal Mar 2022, 59 (3) 2101856; DOI: 10.1183/13993003.01856-2021
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