Ching-Wan Lam1, Chun-Yiu Law2, Kelvin Kai-Wang To3, Stanley Kwok-Kuen Cheung3, Kim-Chung Lee2, Kong-Hung Sze3, Ka-Fai Leung2, Kwok-Yung Yuen3. 1. Department of Pathology, The University of Hong Kong, Hong Kong, China. Electronic address: ching-wanlam@pathology.hku.hk. 2. Department of Pathology, 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: Urinary tract infection (UTI) is one of the most common bacterial infections in humans; however, there is no accurate and fast quantitative test to detect UTI. Dipstick urinalysis is semi-quantitative with a limited diagnostic accuracy, while urine culture is accurate but takes time. We described a quantitative biochemical method for the diagnosis of bacteriuria using a single marker. METHODS: We compared the urine metabolomes from 88 patients with bacterial UTI and 61 controls using (1)H NMR spectroscopy followed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The biomarker identified was subsequently validated using independent samples. RESULTS: The urine acetic acid/creatinine (mmol/mmol) level was determined to be the most discriminatory marker for bacterial UTI with an area-under-receiver operating characteristic curve=0.97, sensitivity=91% and specificity=95% at the optimal cutoff 0.03 mmol/mmol. For validation, 60 samples were recruited prospectively. Using the optimal cutoff for acetic acid/creatinine, this method showed sensitivity=96%, specificity=94%, positive predictive value=92%, negative predictive value=97% and an overall accuracy=95%. The diagnostic performance was superior to dipstick urinalysis or microscopy. In addition, we also observed an increase of urinary trimethylamine (TMA) in patients with Escherichia coli-associated UTI. TMA is a mammalian-microbial co-metabolite and the high level of TMA generated is related to the bacterial enzyme, trimethylamine N-oxide (TMAO) reductase which reduces TMAO to TMA. CONCLUSIONS: Urine acetic acid is a neglected metabolite that can be used for rapid diagnosis of UTI and TMA can be used for etiologic diagnosis of UTI. With the introduction of NMR-based clinical analyzers to clinical laboratories, NMR-based urinalysis can be translated for clinical use.
BACKGROUND:Urinary tract infection (UTI) is one of the most common bacterial infections in humans; however, there is no accurate and fast quantitative test to detect UTI. Dipstick urinalysis is semi-quantitative with a limited diagnostic accuracy, while urine culture is accurate but takes time. We described a quantitative biochemical method for the diagnosis of bacteriuria using a single marker. METHODS: We compared the urine metabolomes from 88 patients with bacterial UTI and 61 controls using (1)H NMR spectroscopy followed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The biomarker identified was subsequently validated using independent samples. RESULTS: The urine acetic acid/creatinine (mmol/mmol) level was determined to be the most discriminatory marker for bacterial UTI with an area-under-receiver operating characteristic curve=0.97, sensitivity=91% and specificity=95% at the optimal cutoff 0.03 mmol/mmol. For validation, 60 samples were recruited prospectively. Using the optimal cutoff for acetic acid/creatinine, this method showed sensitivity=96%, specificity=94%, positive predictive value=92%, negative predictive value=97% and an overall accuracy=95%. The diagnostic performance was superior to dipstick urinalysis or microscopy. In addition, we also observed an increase of urinary trimethylamine (TMA) in patients with Escherichia coli-associated UTI. TMA is a mammalian-microbial co-metabolite and the high level of TMA generated is related to the bacterial enzyme, trimethylamine N-oxide (TMAO) reductase which reduces TMAO to TMA. CONCLUSIONS: Urine acetic acid is a neglected metabolite that can be used for rapid diagnosis of UTI and TMA can be used for etiologic diagnosis of UTI. With the introduction of NMR-based clinical analyzers to clinical laboratories, NMR-based urinalysis can be translated for clinical use.
Authors: Kelvin K W To; Kim-Chung Lee; Samson S Y Wong; Kong-Hung Sze; Yi-Hong Ke; Yin-Ming Lui; Bone S F Tang; Iris W S Li; Susanna K P Lau; Ivan F N Hung; Chun-Yiu Law; Ching-Wan Lam; Kwok-Yung Yuen Journal: Diagn Microbiol Infect Dis Date: 2016-03-14 Impact factor: 2.803
Authors: G B V S Lakshmi; Amit K Yadav; Neha Mehlawat; Rekha Jalandra; Pratima R Solanki; Anil Kumar Journal: Sci Rep Date: 2021-01-14 Impact factor: 4.379
Authors: Andreas Kronenberg; Lukas Bütikofer; Ayodele Odutayo; Kathrin Mühlemann; Bruno R da Costa; Markus Battaglia; Damian N Meli; Peter Frey; Andreas Limacher; Stephan Reichenbach; Peter Jüni Journal: BMJ Date: 2017-11-07