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. 2025 Aug 14;232(2):370-380.
doi: 10.1093/infdis/jiaf072.

Urine Metabolites of Suspected Community-Acquired Pneumonia

Lilliam Ambroggio  1   2 , Todd A Florin  3 , Kayla Williamson  4 , Grace Bosma  4 , Brandie D Wagner  4 , Larisa Yeomans  5   6   7   8 , Jae Hyun Kim  5   6   7   8 , Heidi Sucharew  9 , Maurizio Macaluso  9 , Richard M Ruddy  10 , Kathleen A Stringer  5   6   7   8 , Samir S Shah  11
Affiliations

Urine Metabolites of Suspected Community-Acquired Pneumonia

Lilliam Ambroggio et al. J Infect Dis. .

Abstract

Background: Accurate diagnosis of community-acquired pneumonia (CAP) can be challenging. Clinical findings are nonspecific, and interpretations of chest radiographs have poor interrater reliability. Pilot studies demonstrate the potential for metabolomics to identify metabolite concentrations that differentiate children with CAP from those without. The objective of this study was to expand these findings in a large cohort of children with CAP compared with controls.

Methods: Urine was collected from children, 3 months to 12 years old, with emergency department visits for suspected CAP and community-based controls. Magnetic resonance spectrometry was used to identify and quantify metabolites. A random forest approach developed 3 models discriminating case patients from community-based controls based on (1) clinical signs and symptoms, (2) metabolites, and (3) the combination of both. The area under the receiver operating characteristic curve (AUC) was computed for each model.

Results: Included were 253 case patients and 122 controls. The metabolite-only model had similar discriminatory ability as the combination model (AUC, 0.97 and 0.99, respectively). The discriminating metabolites in the metabolite-only model were 2-aminobutyrate, fumarate, hypoxanthine, acetone, leucine, quinolinate, valine, O-acetylcarnitine, citrate, and trigonelline. In the combined model, discriminatory clinical factors included receipt of corticosteroids, fever, cough, rapid breathing, decreased oral intake, difficulty breathing, receipt of albuterol, abnormal sleepiness, vomiting, and wheezing and included 5 additional metabolites compared with the metabolite-only model (4-hydroxybenzoate, isoleucine, carnitine, 2-hydroxyisovalerate, betaine, and succinate).

Conclusions: Urine metabolite concentrations can accurately discriminate healthy children from children with suspected CAP. Metabolites associated with CAP may overcome limitations of prior diagnostic approaches.

Keywords: biomarkers; controls; metabolomic; pediatric; pneumonia.

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Conflict of interest statement

Potential conflicts of interest. L. A. received grant support through her institution from Pfizer for a urinary diagnostic study that is unrelated to the current work; the populations recruited for the studies are separate. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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