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

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.

Elevated urine IL-10 concentrations associate with Escherichia coli persistence in older patients susceptible to recurrent urinary tract infections.

BACKGROUND: Age is a significant risk factor for recurrent urinary tract (rUTI) infections, but the clinical picture is often confused in older patients who also present with asymptomatic bacteriuria (ASB). Yet, how bacteriuria establishes in such patients and the factors underpinning and/or driving symptomatic UTI episodes are still not understood. To explore this further a pilot study was completed in which 30 male and female community based older patients (mean age 75y) presenting clinically with ASB / rUTIs and 15 control volunteers (72y) were recruited and monitored for up to 6 months. During this period symptomatic UTI episodes were recorded and urines collected for urinary cytokine and uropathogenic Escherichia coli (UPEC) analyses. RESULTS: Eighty-six per cent of patients carried E. coli (102 ≥ 105 CFU/ml urine) at some point throughout the study and molecular typing identified 26 different E. coli strains in total. Analyses of urine samples for ten different cytokines identified substantial patient variability. However, when examined longitudinally the pro-inflammatory markers, IL-1 and IL-8, and the anti-inflammatory markers, IL-5 and IL-10, were significantly different in the patient urines compared to those of the controls (P < 0.0001). Furthermore, analysing the cytokine data of the rUTI susceptible cohort in relation to E. coli carriage, showed the mean IL-10 concentration to be significantly elevated (P = 0.04), in patients displaying E. coli numbers ≥105 CFU/ml. CONCLUSIONS: These pilot study data suggest that bacteriuria, characteristic of older rUTI patients, is associated with an immune homeostasis in the urinary tract involving the synthesis and activities of the pro and anti-inflammatory cytokines IL-1, IL-5, IL-8 and IL-10. Data also suggests a role for IL-10 in regulating bacterial persistence.

Fluids for continuous renal replacement therapy--an evaluation of microbial integrity.

PURPOSE: We have previously demonstrated widespread microbial contamination in the dialysis and replacement fluid circuits of bicarbonate-buffered, continuous renal replacement therapies (CRRTs). It is not known whether different CRRT fluids have an impact on bacterial activity. METHODS: In this study the in vitro growth and biofilm formation associated with seven strains of bacteria (Burkholderia cepacia, Escherichia coli, Staphylococcus aureus, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Pseudomonas fluorescens, and Staphylococcus epidermidis) in five CRRT fluids (Prismocitrate, Monosol S, Accusol 35, tri-sodium citrate and Ci-Ca K2) were studied. The fluids were each inoculated with light and heavy concentrations of each of the bacterial strains and incubated at 22 or 37°C for up to 72 h with and without bacterial growth medium. Bacterial growth was assessed by spectrophotometry. Biofilm formation was assessed by a standard microtiter plate assay. RESULTS: Unsupplemented fluids did not support bacterial growth or biofilm formation after 72 h incubation. When supplemented with bacterial growth medium, some fluids, in particular Accusol 35, Ci-Ca K2, and tri-sodium citrate, had an inhibitory effect on bacterial growth, although none suppressed growths across the panel of tested organisms. CONCLUSIONS: Different CRRT fluids have different impacts on bacterial growth and biofilm formation, but all remain susceptible to extrinsic contamination.

Non cystic fibrosis bronchiectasis: A longitudinal retrospective observational cohort study of Pseudomonas persistence and resistance.

BACKGROUND: The hallmark of non-cystic fibrosis bronchiectasis is recurrent bronchial infection, yet there are significant gaps in our understanding of pathogen persistence, resistance and exacerbation frequencies. Pseudomonas aeruginosa is a key pathogen thought to be a marker of disease severity and progression, yet little is known if the infection risk is seen in those with milder disease or if there is any potential for eradication. These data are important in determining risk stratification and follow up. METHODS AND PATIENT COHORT: A retrospective review of consecutive adult patients attending a specialist UK bronchiectasis clinic over a two-year recruitment period between July 2007 and June 2009 was performed. Analysis of our primary outcome, longitudinal microbiological status, was recorded based on routine clinical follow-up through to data capture point or date of death. Patients were stratified by lung function and infecting organism. RESULTS: 155 patients (mean (SD) age 62.2 (12.4) years; 60.1% female) were identified from clinic records with microbiological data for a median (IQR) follow up duration of 46 (35-62) months. Baseline mean FEV1% predicted was 60.6% (24.8) with mean exacerbation frequency of 4.42/year; 73.6% reported 3 or more exacerbations/year. Haemophilus influenzae was isolated in 90 (58.1%) patients and P. aeruginosa in 78 (50.3%) patients with persistent infection in 51 (56.7%) H. influenzae and 47 (60.3%) P. aeruginosa, respectively. Of the P. aeruginosa colonised patients, 16 (34%) became culture negative on follow-up with a mean of 5.2 negative sputum cultures/patient. P. aeruginosa was isolated from 5 out of 39 patients (12.8%) with minimal airflow limitation as compared to 18 out of 38 patients (47.4%) with severe airflow limitation. Although hospital admissions were significantly higher in the P. aeruginosa infected group (1.3 vs. 0.7 admissions per annum, p = 0.035), overall exacerbation rates were the same (4.6 vs. 4.3, p = 0.58). Independent predictors of P. aeruginosa colonisation were low FEV1% predicted (OR 2.46; 95% CI 1.27-4.77) and polymicrobial colonisation (OR 4.07; 95% CI 1.56-10.58). 17 (11%) patients were infected with multi-resistant strains; however, none were pan-resistant. CONCLUSIONS: P. aeruginosa is associated with greater persistent infection rates and more hospital admissions than H. influenzae. Exacerbation rates, however, were similar; therefore H. influenzae causes significant out-patient morbidity. P. aeruginosa infection occurs across all strata of lung function impairment but is infrequently multi-resistant in bronchiectasis. Careful microbiology follow up is required even in those with well-preserved lung function.