Urine resazurin reduction ratio as a biomarker of urinary tract infection in people with neurogenic bladder: A first in human study

Abstract

Among people with neurogenic lower urinary tract dysfunction (NLUTD), urinary tract infection (UTI) is the most common infection and a leading cause of morbidity. UTI diagnosis is based on urinary symptoms, bladder inflammation (urinalysis (UA)), and bacterial growth (standard urine culture (SUC)), the latter two assessments taking approximately 24h and 48-72h, respectively. Here, urine resazurin reduction ratio (uRRR), which is a measure of nicotinamide adenine dinucleotide hydrogen conversion, a bioproduct of bacterial metabolism, is assessed as a point-of-care biomarker of UTI with time to result (TTR) of 1 hour. The objectives of this first-in-human study are to evaluate the relationship between the uRRR and: urinary symptoms, urine white blood cell (uWBC) count, urine nitrite, bacterial growth on standard urine culture (SUC), and the likelihood of UTI based on combinations of these. This is a cross-sectional study of participants who completed the Urinary Symptom Questionnaire for people with Neurogenic Bladder (USQNB) and provided urine samples (N = 289). Accuracy of uRRR when compared to colony forming units per milliliter (CFU/mL) obtained by SUC was 92.73%. A significant relationship was found between higher uRRR and positive uWBC (p < 0.0001), positive nitrite (p < 0.0001), and symptoms (p < 0.0001). uRRR values were significantly higher in the UTI positive group, which was defined as a combination of positive symptoms, bladder inflammation, and bacterial growth. In this first report of uRRR as a potential biomarker and rapid diagnostic assessment of UTI among people with NLUTD, uRRR was associated with each of the standard of care diagnostic assessments individually and when combined into UTI likelihood groups. Given these encouraging preliminary data, next steps will be to assess uRRR in a prospective clinical trial to determine whether point-of-care uRRR provides clinically actionable information equivalent or superior to standard of care assessments when diagnosing and treating suspected UTI in this population.