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Clin Chim Acta. 2015 Jan 1;438:24-8. doi: 10.1016/j.cca.2014.07.038. Epub 2014 Aug 6.

Quantitative metabolomics of urine for rapid etiological diagnosis of urinary tract infection: evaluation of a microbial-mammalian co-metabolite as a diagnostic biomarker.

Author information

1
Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. Electronic address: ching-wanlam@pathology.hku.hk.
2
Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
3
Research Centre of Infection and Immunology, Hong Kong, China; State Key Laboratory for Emerging Infectious Diseases, Hong Kong, China; Department of Microbiology, The University of Hong Kong, Hong Kong, China.

Abstract

BACKGROUND:

We have previously reported a NMR-based urinalysis for the screening of urinary tract infection (UTI) with high accuracy and reproducibility. Urinary acetic acid per creatinine was found to be a diagnostic marker of bacterial UTI with an area-under-receiver operating characteristic (ROC) curve of 0.97. In addition, we identified trimethylamine (TMA) as a human-microbial marker of Escherichia coli (EC)-associated UTI. Here, we evaluate the clinical application of NMR-based urinalysis in aiding the etiological diagnosis of bacterial UTI.

METHODS:

Proton NMR spectroscopy was acquired using a Bruker 600MHz spectroscopy for 88 urine samples from patients with bacterial UTI, confirmed by urine culture. The spectra were analyzed using orthogonal partial least squares-discriminant analysis (OPLS-DA). ROC curve analysis was performed after the quantitation of the urine metabolites.

RESULTS:

The TMA/creatinine (mmol/mmol) level was determined to be a specific marker for EC-associated UTI. It has an area-under-ROC=0.85 (95% confidence interval: 0.75-0.91). For the etiological diagnosis, the cutoff for 97.0% specificity was at 0.0117mmol/mmol creatinine for EC-associated UTI with a sensitivity of 66.7%. The mean of TMA/creatinine of EC is 21-fold that of non-EC.

CONCLUSIONS:

The co-metabolism of TMA by EC and human cells makes TMA an ideal urine biomarker for UTI. The presence of TMA in a freshly collected sample eliminates the possibility of contamination of urine by bacteria during the collection process resulting in a positive bacterial culture result. We envisage the NMR-based urinalysis of urinary TMA that can be a useful method for the etiological diagnosis of EC-associated UTI.

KEYWORDS:

Co-metabolites; Escherichia coli; NMR spectroscopy; Quantitative metabolomics; Trimethylamine; Urinary tract infection

PMID:
25108210
DOI:
10.1016/j.cca.2014.07.038
[Indexed for MEDLINE]

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