Identification of clinical and urine biomarkers for uncomplicated urinary tract infection using machine learning algorithms

• Published in: Scientific reports 2019-12, Vol.9 (1), p.19694-11, Article 19694
• Main Authors: Gadalla, Amal A. H., Friberg, Ida M., Kift-Morgan, Ann, Zhang, Jingjing, Eberl, Matthias, Topley, Nicholas, Weeks, Ian, Cuff, Simone, Wootton, Mandy, Gal, Micaela, Parekh, Gita, Davis, Paul, Gregory, Clive, Hood, Kerenza, Hughes, Kathryn, Butler, Christopher, Francis, Nick A.
• Format: Article
• Language: English
• Subjects: 13; 13/21; 692/53/2421; 692/699/255/1318; Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Antibiotics; Antimicrobial resistance; Biomarkers; Biomarkers - urine; Diagnosis, Computer-Assisted; Female; Gelatinase B; Humanities and Social Sciences; Humans; IL-1β; Immunologic Factors - urine; Immunology; Interleukin-1beta - urine; Interleukin-8 - urine; Learning algorithms; Likelihood Functions; Lipocalin-2 - urine; Machine Learning; Matrix Metalloproteinase 9 - urine; Middle Aged; multidisciplinary; Nephelometry and Turbidimetry; Point-of-Care Testing; Science; Science (multidisciplinary); Support Vector Machine; Turbidity; Urinary tract; Urinary tract diseases; Urinary tract infections; Urinary Tract Infections - diagnosis; Urinary Tract Infections - immunology; Urinary Tract Infections - urine; Urine; Urogenital system; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-55523-x

Women with uncomplicated urinary tract infection (UTI) symptoms are commonly treated with empirical antibiotics, resulting in overuse of antibiotics, which promotes antimicrobial resistance. Available diagnostic tools are either not cost-effective or diagnostically sub-optimal. Here, we identified clinical and urinary immunological predictors for UTI diagnosis. We explored 17 clinical and 42 immunological potential predictors for bacterial culture among women with uncomplicated UTI symptoms using random forest or support vector machine coupled with recursive feature elimination. Urine cloudiness was the best performing clinical predictor to rule out (negative likelihood ratio [LR−] = 0.4) and rule in (LR+ = 2.6) UTI. Using a more discriminatory scale to assess cloudiness (turbidity) increased the accuracy of UTI prediction further (LR+ = 4.4). Urinary levels of MMP9, NGAL, CXCL8 and IL-1β together had a higher LR+ (6.1) and similar LR− (0.4), compared to cloudiness. Varying the bacterial count thresholds for urine culture positivity did not alter best clinical predictor selection, but did affect the number of immunological predictors required for reaching an optimal prediction. We conclude that urine cloudiness is particularly helpful in ruling out negative UTI cases. The identified urinary biomarkers could be used to develop a point of care test for UTI but require further validation.