The 2024 International Consensus Reference Standard for Urinary Tract Infection (UTI) Research fails in Neurogenic Bladder without UTI symptoms

Abstract Background The 2024 international reference standard for urinary tract infection (UTI) research scores four domains - symptoms and signs, systemic criteria, pyuria, and culture - to classify samples as No UTI, Possible UTI, Probable UTI, or Definite UTI. It identifies spinal cord injury (SCI) as a condition of impaired symptom perception, and states that catheter-associated UTI requires a separate standard. We applied it to confirmed-asymptomatic samples from adults with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury or disease (SCI/D) who use intermittent catheterization (IC). Methods The reference standard was applied to 222 samples from 96 adults with NLUTD due to SCI/D using IC, for all of which the participant confirmed, using the Urinary Symptom Questionnaire for Neurogenic Bladder–Intermittent Catheter (USQNB-IC), that they had been asymptomatic at sampling and for 72 hours prior. Because no participant was febrile and no blood markers are drawn in this population, the systemic-criteria domain scored zero for every sample; the reported classifications are therefore a floor. Pyuria was scored under conservative and inclusive interpretations of categorical urinary white blood cell (WBC) bins. Results Under the conservative interpretation, 38.7% of samples were classified No UTI, 22.5% Possible UTI, and 38.7% Probable UTI; under the inclusive interpretation, 8.1% No UTI, 40.5% Possible UTI, and 51.4% Probable UTI. No sample reached Definite UTI, a structural consequence of the empty systemic domain. Of the samples that met the pyuria entry threshold, 136 of 136 (conservative) and 204 of 206 (inclusive) were classified Possible or Probable UTI: meeting the entry threshold determined the classification. Conclusions The consensus reference standard classifies 61–92% of confirmed-asymptomatic NLUTD-IC samples as Possible or Probable UTI, and 39–51% as Probable UTI - a floor estimate that could only rise if blood markers were available. This confirms the framework’s own prediction that a separate standard is needed for populations with altered symptom expression and baseline-positive urinary markers. Research in context Evidence before this study Urinary tract infection (UTI) is the most common secondary condition and infectious cause of hospitalisation among people with neurogenic lower urinary tract dysfunction due to spinal cord injury or disease, and it is over-diagnosed and over-treated in this population. Diagnosis has long rested on laboratory thresholds - pyuria and bacteriuria - despite repeated demonstrations that both are common in people who do not have or develop symptoms, and that neither is associated with symptom status in those who catheterize. In 2024 an international multidisciplinary Delphi consensus published a reference standard for UTI research that scores four domains, states that it systematically addressed all issues of diagnosis and nomenclature for research purposes, and extends explicitly to populations unable to perceive or express lower urinary tract symptoms, naming spinal cord injury as one such population. That standard has not, to our knowledge, been applied to people in this population whose symptom status was known, and no published study has examined whether the reference standard can be applied based on the results in routine clinical laboratory reports. Added value of this study We applied the reference standard to 222 urine samples from 96 community-dwelling adults with neurogenic lower urinary tract dysfunction who use intermittent catheterisation, each of whom confirmed, using an instrument validated in this population, that they had been asymptomatic for the 72 hours before the sample was taken. The standard assigns one point toward a UTI classification to individuals with spinal cord injury without requiring them to endorse any specific symptom, and in this group of asymptomatic individuals, between 61% and 92% of their samples were classified as Possible or Probable UTI. The range of misclassification depends on how the pyuria criteria are applied: a large clinical laboratory provides leukocyte counts in bins that overlap the reference standard criteria at the low (0-5 per hpf) and high (40-60 per hpf) ends, whereas a research laboratory might instead provide exactly the values requested. Implications of all the available evidence A reference standard intended to define UTI for research is intended for selecting participants, adjudicating patient and research outcomes, and auditing practice. If it classifies the majority of samples from people who report no symptoms as Possible or Probable UTI, it will inflate apparent infection rates, systematically misclassify controls, and give the appearance of evidence to treatment decisions that the underlying data do not support. This is demonstrated within a population already subject to substantial antimicrobial over-use, those with neurogenic lower urinary tract dysfunction due to spinal cord injury or disease. Two remedies follow directly. The capability question should be answered from the patient, using instruments that are validated for the patient’s primary method of bladder management, rather than from the diagnosis; and any standard intended for routine as well as research settings should be scoreable from the results laboratories actually issue, with explicit instructions for categorical bins that straddle its thresholds and for results that are categorical rather than quantitative.