Abstract

BackgroundIdentifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease’s complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques.ResultsWe conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical metagenomics assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes.ConclusionsClinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP.Trial registrationTrial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628.

Highlights

  • Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease’s complex etiology and the limitations of traditional microbiological diagnostic methods

  • Patients who met the following criteria (1 + 2) and at least one of the criteria (3)–(7) were enrolled this prospective study and randomly assigned into either the control or metagenomic next-generation sequencing (mNGS) groups with informed consents signed by patients or surrogates: (1) Admitted at our Intensive Care Unit (ICU) and considered for pneumonia acquired outside of the hospital setting; (2) A new or progressive pulmonary infiltration with/without pleural effusion on a chest radiograph; (3) New or increased cough with or without sputum production; (4) Purulent sputum or a change in sputum characteristics; (5) Fever; (6) Signs of lung consolidation or moist rales; (7) Peripheral white blood cell (WBC) count ≥10 × 109/L or ≤ 4 × 109/L

  • We evaluated the impact of mNGS-based testing on clinical management and outcomes by categorizing each patient’s clinical outcome into three groups as of his/her last day in the Intensive Care Unit (ICU): Improved, Resolved, or Average age

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Summary

Introduction

Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease’s complex etiology and the limitations of traditional microbiological diagnostic methods. Community-acquired pneumonia (CAP) is one of the most common and morbid conditions encountered in clinical practice [1,2,3,4,5]. Some pathogens such as Streptococcus pneumoniae [6] are commonly detected in CAP patients, over 100 bacterial, viral, fungal, and parasitic causes of CAP have been reported [7]. Since its first reported clinical application in 2014, metagenomic next-generation sequencing (mNGS) has shown promise for the diagnosis of infectious diseases due to its ability to identify multiple pathogens by a single assay [11,12,13].

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