a A longitudinal study of long-term Escherichia coli colonisation of the elderly bladder

Abstract

Urinary tract infections (UTIs) are the second most common cause of infection worldwide, making them a huge economic burden. People can carry diagnostic loads of bacteria within the bladder without experiencing any symptoms, this is asymptomatic bacteriuria (ABU). ABU prevalence increases with age, with around 19% of those over 60 being susceptible. ABU can reactivate sporadically, causing symptomatic episodes, known as recurrence. Current treatment is with antibiotics, either short courses or prophylaxis. Guidelines state to only treat symptomatic episodes. However, UTI symptoms are often diffuse and unclear, especially in older people. Thus, ABU is inappropriately treated in up to 52% of cases, encouraging antibiotic resistance. Better ways of discriminating between symptomatic and asymptomatic cases are needed. This would allow for more efficient treatment and patient management. To improve understanding of ABU, a longitudinal clinical pilot study was performed. For 6 months, every 2 weeks a urine sample and symptom questionnaire was collected from 30 patients over 65 who were clinically diagnosed with recurrent UTIs. The aim was to analyse potential changes in the host response and the colonising bacteria around periods of symptoms to see if distinct urinary profiles could be seen between symptomatic and asymptomatic states. Allowing for analysis into potential predictive biomarkers for symptoms. Uropathogenic Escherichia coli (UPEC) is known to cause the majority of UTIs, thus was the bacterial focus for this project. The study firstly allowed us to test the feasibility of such a demanding study design. It was possible to fully recruit to the study with all 30 patients completing its entirety, thus suggesting such a design could be repeated or scaled up in the future. The study produced a large database of bacterial isolates as well as urine samples. Urines were measured for a wide range of immune response proteins. Despite varying levels of immune activation, UPEC was able to evade host-defences and thrive in the bladder long-term. The study showed that ABU patients can carry significant bacterial loads of UPEC, even with antibiotics, questioning the advantages of prophylactic treatment of ABU patients. No distinct host or bacterial profile was identified between symptomatic states. No biomarkers could be seen to predict symptomatic episodes in these patients. However, what was observed was an unexpected level of dynamic variability within individuals and across the patient cohort.c