Abstract
Diagnosis of microbial disease etiology in community-acquired pneumonia (CAP) remains challenging. We undertook a large-scale metabolomics study of serum samples in hospitalized CAP patients to determine if host-response associated metabolites can enable diagnosis of microbial etiology, with a specific focus on discrimination between the major CAP pathogen groups S. pneumoniae, atypical bacteria, and respiratory viruses. Targeted metabolomic profiling of serum samples was performed for three groups of hospitalized CAP patients with confirmed microbial etiologies: S. pneumoniae (n = 48), atypical bacteria (n = 47), or viral infections (n = 30). A wide range of 347 metabolites was targeted, including amines, acylcarnitines, organic acids, and lipids. Single discriminating metabolites were selected using Student's T-test and their predictive performance was analyzed using logistic regression. Elastic net regression models were employed to discover metabolite signatures with predictive value for discrimination between pathogen groups. Metabolites to discriminate S. pneumoniae or viral pathogens from the other groups showed poor predictive capability, whereas discrimination of atypical pathogens from the other groups was found to be possible. Classification of atypical pathogens using elastic net regression models was associated with a predictive performance of 61% sensitivity, 86% specificity, and an AUC of 0.81. Targeted profiling of the host metabolic response revealed metabolites that can support diagnosis of microbial etiology in CAP patients with atypical bacterial pathogens compared to patients with S. pneumoniae or viral infections.
Highlights
Community-acquired pneumonia (CAP) is a commonly occurring respiratory tract infection caused by bacterial or viral pathogens that can lead to severe disease, especially in elderly patients [1]
Targeted profiling of the host metabolic response revealed metabolites that can support diagnosis of microbial etiology in CAP patients with atypical bacterial pathogens compared to patients with S. pneumoniae or viral infections
The patients were diagnosed with the microbial etiology S. pneumoniae (n = 48), atypical bacteria (n = 47), or respiratory virus (n = 30) (Table 2)
Summary
Community-acquired pneumonia (CAP) is a commonly occurring respiratory tract infection caused by bacterial or viral pathogens that can lead to severe disease, especially in elderly patients [1]. The predominant pathogens found in hospitalized CAP patients are Streptococcus pneumoniae and to a lesser extent, Haemophilus influenzae, Legionella pneumophila, and respiratory viruses [2, 3]. Broad-spectrum antibiotics are over-used, which facilitates the emergence of antimicrobial resistance [7, 8]. To this end, a need exists to explore innovative methods to enhance the diagnostic performance for the detection of microbial pathogens in CAP
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