Urine Collection and Novel UTI Biomarkers in Children and Older Adults

Background:

Urinary tract infection (UTI) is one of the most common bacterial infections requiring medical assessment in young children and older adults. Accurate diagnosis is particularly challenging at the extremes of age, where patients frequently present with non-specific symptoms and current urine diagnostic tests perform poorly. In young children, contamination of urine samples collected using non-invasive methods often results in false-positive urine cultures, while in older adults the high prevalence of asymptomatic bacteriuria (ASB) makes it difficult to distinguish bacterial colonisation from true infection. These diagnostic limitations contribute to unnecessary antibiotic prescribing, avoidable hospital admissions and increased antimicrobial resistance. This study aims to evaluate novel urinary host and bacterial biomarkers to improve the diagnosis of UTI by distinguishing true infection from contamination in children and from ASB in older adults.

Objectives:

Primary Objectives:

• Determine the diagnostic accuracy (sensitivity, specificity and AUC) of urinary host biomarkers for diagnosing paediatric UTI across different urine collection methods.
• To characterise the molecular features of urine samples from children with different microbiological classifications of urinary tract infection.
• To characterise the molecular features of urine samples from older adults with symptomatic urinary tract infection and asymptomatic bacteriuria.

Study Design:

A prospective observational study conducted in the Emergency Departments of the Royal Belfast Hospital for Sick Children and the Royal Victoria Hospital. The paediatric component comprises a diagnostic accuracy cohort study with a nested case-control transcriptomic study, while the adult component is a case-control study comparing symptomatic UTI with asymptomatic bacteriuria.

Study Population:

Children under 5 years of age who are not toilet trained and have urine sent for culture for suspected UTI, and adults aged 65 years and over undergoing urine culture for suspected UTI in the Emergency Department. Participants must have sufficient residual urine remaining following routine clinical testing. Exclusion criteria include inability to obtain consent and antibiotic treatment within the preceding 48 hours.

Setting:

Royal Belfast Hospital for Sick Children Emergency Department and Royal Victoria Hospital Emergency Department, Belfast.

Screening:

Potential participants will be identified by the clinical care team. Following informed consent, clinical information and laboratory results will be recorded on a case report form (CRF), with clinical outcomes reviewed 14 days after presentation.

Procedures:

Residual urine samples collected during routine clinical care will be retained following consent. Where available, residual plasma from routine blood sampling may also be stored. No additional urine collection or phlebotomy will be performed for research purposes. Samples will be pseudonymised, transported to Queen's University Belfast for storage and analysis, and used for urinary biomarker measurement, bacterial RNA sequencing and bacterial isolate banking.

Reference Standards:

In children, UTI will be defined using predefined urine culture thresholds according to urine collection method. Samples selected for bacterial RNA sequencing may include urine from children with confirmed UTI, contaminated urine samples and, where available, healthy control samples. In older adults, symptomatic UTI and asymptomatic bacteriuria will be classified using documented urinary symptoms together with urine culture results according to established guideline criteria.

Inclusion criteria

Children:

• Children under 5 years of age who are not toilet trained.
• Urine dipstick positive for nitrates or leukocytes (including trace).
• Residual urine sample remaining following completion of all routine clinical urine testing.

Older Adults:

• Adults aged 65 years and over.
• Urine dipstick positive for nitrates or leukocytes (including trace).
• Residual urine sample remaining following completion of all routine clinical urine testing.

Exclusion criteria

• Consent declined.
• Inability to obtain informed consent.
• Antibiotic treatment within the previous 48 hours for acute infection.