Multidrug-resistant Uro-associated Escherichia coli Populations and Recurrent Urinary Tract Infections in Patients Performing Clean Intermittent Self-catheterisation

Catherine Mowbray; Aaron Tan; Maxime Vallée; Holly Fisher; Thomas Chadwick; Catherine Brennand; Katherine E Walton; Robert S Pickard; Christopher Harding; Phillip D Aldridge; Judith Hall

doi:10.1016/j.euros.2021.12.015

Multidrug-resistant Uro-associated Escherichia coli Populations and Recurrent Urinary Tract Infections in Patients Performing Clean Intermittent Self-catheterisation

Eur Urol Open Sci. 2022 Feb 2:37:90-98. doi: 10.1016/j.euros.2021.12.015. eCollection 2022 Mar.

Authors

Affiliations

¹ Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
² Department of Urology, Poitiers University Hospital, Poitiers, France.
³ Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
⁴ Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK.
⁵ Department of Microbiology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
⁶ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
⁷ Urology Department, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Abstract

Background: The AnTIC trial linked continuous low-dose antibiotic prophylaxis treatments to a lower incidence of symptomatic urinary tract infections (UTIs) among individuals performing clean intermittent self-catheterisation (CISC).

Objective: To explore potential mechanisms underlying the protective effects of low-dose antibiotic prophylaxis treatments, blood and urine samples and uro-associated Escherichia coli isolates from AnTIC participants were analysed.

Design setting and participants: Blood samples (n = 204) were analysed for TLR gene polymorphisms associated with UTI susceptibility and multiple urine samples (n = 558) were analysed for host urogenital responses. E.coli sequence data for 45 temporal isolates recovered from the urine samples of 16 trial participants in the prophylaxis (n = 9) and no-prophylaxis (n = 7) study arms, and characterised by multidrug resistance (MDR), were used to classify individual strains.

Outcome measurements and statistical analysis: TLR polymorphism data were analysed using Poisson regression. Concentrations of urine host defence markers were analysed using linear mixed-effects models, which accounted for repeated urine samples.

Results and limitations: Urine samples from CISC users, irrespective of antibiotic treatment regimens, were associated with robust urothelial innate responses. No links were identified between TLR genotype and CISC user susceptibility to recurrent UTIs. Microbiological study data were limited to the predominant MDR E. coli population; participants prescribed low-dose prophylactic antibiotics were predominantly colonised by a single uro-associated E. coli strain, while participants given acute antibiotic treatments were each colonised by more than one E. coli strain.

Conclusions: Antibiotic treatments did not impact urogenital responses to infection in CISC users. Host genetics in terms of TLR polymorphisms played no role in determining CISC user susceptibility to or protection from recurrent UTIs. Prophylactic antibiotic treatments associated with MDR E. coli were associated with colonisation by stable uro-associated E. coli genotypes.

Patient summary: Our findings show that the natural urogenital defences of clean intermittent self-catheterisation (CISC) users were not impacted by antibiotic treatments. For some CISC users, prophylaxis with low-dose antibiotics selected for a stable, predominantly, Esherichia coli rich uromicrobiota.

Keywords: Antibiotics; Continuous intermittent single-use catheterisation; Escherichia coli; Innate immunity; Lower urinary tract infection; Multidrug resistance; Prophylaxis; TLR genotype; TLR genotype, Toll-like Receptor genotype.