Metabolomics strategy for diagnosing urinary tract infections

Abstract

AbstractMetabolomics has emerged as a mainstream approach for investigating complex metabolic phenotypes. Despite its obvious suitability to diagnostics, it has yet to be integrated into routine clinical laboratory applications. Metabolomics-based diagnosis of infectious diseases is a logical application of this technology since microbial metabolic waste products are concentrated at the site of infection. In the case of urinary tract infections (UTIs), one of the most common bacterial infections, microbial catabolites are trapped in the bladder and thus could enable rapid diagnosis of UTIs. We conducted an untargeted metabolomics screen of 110 clinical specimens and identified two metabolites, agmatine and N6-methyladenine, that are predictive of a wide transect of pathogen species that collectively account for over 90% of UTI infections. We showed that these metabolites were consistently observed in multiple independent cohorts, including a blinded trial of over 587 clinical specimens (95% sensitivity, 86% specificity; PPV, 0.68; NPV, 0.98). These findings demonstrate the potential utility of metabolomics for diagnosing infectious diseases. Moreover, the rapid analysis times enabled through our metabolomics diagnostic approach—six minutes per sample—could curtail the inappropriate UTI clinical prescribing practices that are currently contributing to the selection of antimicrobial resistance.Significance statementWe show that a six-minute metabolomics assay robustly identifies most UTIs based on the presence of two microbial catabolites present in the urine. We demonstrate the potential clinical utility of this strategy in a prospective blinded trial. If implemented in clinical practice, this diagnostic approach could shorten laboratory testing times for UTIs by 18 hours and could improve antimicrobial stewardship.