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

Author:

Pereverzeva LizaORCID,Uhel Fabrice,Sengers Hessel PetersORCID,Butler Joe,van Vught Lonneke A.,Burnham Katie L.ORCID,Davenport Emma E.,Knight Julian C.,Cremer Olaf L.,Schultz Marcus J.,Bonten Marc M. J.,Scicluna Brendon P.,van der Poll Tom

Abstract

BackgroundGram-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.MethodsSixteen host response biomarkers providing insight in 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.Results309 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 leukocytes 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.ConclusionOutcome and host response are similar in critically ill patients with CAP due to Gram-positive bacteria compared to Gram-negative bacteria.

Funder

Center for Translational Molecular Medicine

Publisher

European Respiratory Society (ERS)

Subject

Pulmonary and Respiratory Medicine

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