Table 1_Distinct systemic metabolic phenotypes associated with blood culture positivity and bacterial etiology in community-acquired pneumonia (CAP).docx

Multivariate and univariate analyses were applied to identify discriminating metabolic features.</p>Results<p>Distinct metabolic phenotypes were observed between culture-positive and culture-negative patients across all platforms. OPLS-DA models demonstrated significant discrimination, with GC-MS and 1H-NMR showing strong internally cross-validated discriminatory performance (Q² > 0.45, AUROC > 0.90). Culture-positive CAP was characterized by increased phenylalanine, urea, and mannose, alongside decreased amino acids and fatty acids, indicating coordinated alterations in nitrogen metabolism, energy pathways, and lipid remodeling.

Furthermore, metabolomic profiles enabled discrimination of Streptococcus pneumoniae from other bacterial causes, with GC-MS and LC-DIMS/MS achieving strong internal discrimination (Q² ≈ 0.4, AUROC > 0.90).</p>Conclusions<p>Plasma metabolomics identified distinct systemic metabolic patterns associated with blood culture positivity and, in exploratory analysis, with S. pneumoniae etiology. These discovery-stage findings demonstrate reproducible systemic metabolic patterns associated with blood culture positivity and bacterial etiology and support further validation of targeted metabolite signatures in independent CAP cohorts.</p>