YELLOW RoUTIne prospective cohort study protocol: insight in the dynamics of bacteria in the elderly bladder.

Background: Asymptomatic bacteriuria (ASB) - the presence of bacteria in urine without urinary tract infection (UTI) related signs & symptoms (S&S) - is common in the elderly bladder and is not considered pathogenic for UTI. We hypothesise that colonisation with non-uropathogenic bacteria could protect the bladder from invasion of more harmful bacteria. The exact role and dynamics of bacteriuria in the relation to the development of a UTI is still unknown. We aim to provide insight into the course of bacteriuria in the elderly bladder and its relation to UTI in frail older adults.

Methods and analysis: A prospective observational cohort study is being conducted in Dutch nursing homes (NHs) between February 2024 and December 2025. Urine samples and case report forms (CRF) on UTI-related S&S will be collected from each consenting NH resident every 3 months for a follow-up period of 18 months. Whenever a UTI-suspicion occurs in between the 3 monthly time points, additional data and a urine sample will be collected. Urine samples undergo several urinalyses (e.g. dipstick and bacterial culture). Additional molecular analysis will be conducted on a selection of cultured Escherichia coli (E. coli) for virulence genes. Primary analyses will be conducted between residents with and without ASB at each time point. The primary outcome is UTI incidence during follow-up. In secondary analyses we will also take into account the low versus high presence of virulence genes of the E. coli.

Discussion: The combination of high ASB prevalence and a reduced ability of frail older adults to express UTI-related S&S may lead to UTI misdiagnosis and inappropriate antibiotic use. To our knowledge, this is the first study to investigate the dynamics and role of bacteriuria in the elderly bladder and their potential protective effect on the development of UTI. The study findings with comprehensive analysis of epidemiological, clinical and molecular data could set the fundamental base for future guidelines and studies, and contribute to improving prevention, diagnosis and treatment of UTI in frail older adults, in addition to contributing to antibiotic stewardship in NHs.