Whole-genome characterisation of Escherichia coli isolates from older women with urinary tract infection and asymptomatic bacteriuria.

BackgroundPre-existing lower urinary tract symptoms (LUTS), cognitive impairment, and the high prevalence of asymptomatic bacteriuria (ASB) complicate the diagnosis of urinary tract infection (UTI) in older women. The presence of pyuria remains the cornerstone of UTI diagnosis. However, >90% of ASB patients have pyuria, prompting unnecessary treatment. We quantified pyuria by automated microscopy and flowcytometry to determine the diagnostic accuracy for UTI and to derive pyuria thresholds for UTI in older women.MethodsWomen ≥65 years with ≥2 new-onset LUTS and 1 uropathogen ≥104 colony-forming units (CFU)/mL were included in the UTI group. Controls were asymptomatic and classified as ASB (1 uropathogen ≥105 CFU/mL), negative culture, or mixed flora. Patients with an indwelling catheter or antimicrobial pretreatment were excluded. Leukocyte medians were compared and sensitivity–specificity pairs were derived from a receiver operating characteristic curve.ResultsWe included 164 participants. UTI patients had higher median urinary leukocytes compared with control patients (microscopy: 900 vs 26 leukocytes/µL; flowcytometry: 1575 vs 23 leukocytes/µL; P < .001). Area under the curve was 0.93 for both methods. At a cutoff of 264 leukocytes/µL, sensitivity and specificity of microscopy were 88% (positive and negative likelihood ratio: 7.2 and 0.1, respectively). The commonly used cutoff of 10 leukocytes/µL had a poor specificity (36%) and a sensitivity of 100%.ConclusionsThe degree of pyuria can help to distinguish UTI in older women from ASB and asymptomatic controls with pyuria. Current pyuria cutoffs are too low and promote inappropriate UTI diagnosis in older women.Clinical Trials Registration. International Clinical Trials Registry Platform: NL9477 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL9477)

Urinary Tract Infections in Solid Organ Transplant Recipients

Background: The incidence of asymptomatic bacteriuria (ABU) increases with age and is most common for persons 80 years of age and above and in elderly living in nursing homes. The distinction between ABU and urinary tract infection (UTI) is often difficult, especially in individuals, who are unable to communicate their symptoms, and there is a lack of objective methods to distinguish between the two entities. This can lead to overuse of antibiotics, which results in the selection and dissemination of antibiotic resistant isolates. Materials and methods: From voided midstream urine samples of 211 participants ≥60 years old from nursing homes, an activity center and a general practitioners clinic, we collected 19 ABU, 16 UTI and 22 control urine samples and compared them with respect to levels of complement component C3 in urine as determined by an ELISA assay relative to creatinine levels in the same urine samples, as measured by a creatinine assay. Further, we studied all Escherichia coli isolates for selected virulence genes by multiplex PCR, and by whole-genome sequencing (WGS) for genotypes and phylogenetic clustering. Antibiotic susceptibility was determined by microtiter broth dilution. Results: We identified a prevalence of ABU of 18.9% in nursing home residents, whereas ABU was only found in 4% of elderly living in the community (p < 0.001). E. coli from ABU patients were significantly more antibiotic resistant than E. coli from UTIs (p = 0.01). Prevalence of classical virulence genes, detected by multiplex PCR, was similar in E. coli isolates from ABU and UTI patients. Whole-genome sequencing of the E. coli isolates showed no specific clustering of ABU isolates compared to UTI isolates. Three isolates from three different individuals from one of the nursing homes showed signs of transmission. We demonstrated a significantly increased level of C3/creatinine ratio in ABU and UTI samples compared to healthy controls; however, there was no significant difference between the ABU and UTI group with respect to C3 level, or virulence factor genes. Conclusion: ABU was significantly more prevalent in the elderly residing in nursing homes than in the elderly living at home. Antibiotic resistance was more prevalent in E. coli from nursing homes than in UTI isolates, but there was no difference in prevalence of virulence associated genes between the two groups and no phylogenetic clustering, as determined by WGS relative to the two types of E. coli bacteriuria. The similar complement C3 response in ABU and UTI patients may indicate that ABU should be reconsidered as an infection albeit without symptoms.

Virulence versus fitness determinants in Escherichia coli isolated from asymptomatic bacteriuria in healthy nonpregnant women

Virulence factors of uropathogenic Escherichia coli of urinary tract infections and asymptomatic bacteriuria in children

BackgroundThe prevalence of type 2 diabetes mellitus (T2DM) is increasing each year and has become one of the most prominent health concerns worldwide. Patients with T2DM are prone to infectious diseases, and urinary tract infections are also widespread. Despite a comprehensive understanding of urinary tract infection (UTI), there is a lack of research regarding primary prevention strategies for asymptomatic bacteriuria (ASB).ObjectiveTo clarify the incidence and risk factors of asymptomatic urinary tract infection in patients with T2DM by meta-analysis to provide evidence for preventing UTI. Help patients, their families, and caregivers to identify the risk factors of patients in time and intervene to reduce the incidence of ASB in patients with T2DM. Fill in the gaps in existing research.Study designMeta-analyses were conducted in line with PRISMA guidelines.MethodsEleven databases were systematically searched for articles about ASB in T2DM, and the retrieval time was selected from the establishment of the database to February 5, 2023. Literature screening, quality evaluation, and meta-analysis were independently performed by two researchers according to the inclusion and exclusion criteria, and a meta-analysis was performed using Stata 17.0.ResultsFourteen articles were included, including cohort and case–control studies. A meta-analysis of 4044 patients with T2DM was included. The incidence of ASB in patients with T2DM was 23.7%(95% CI (0.183, 0.291); P < 0.001). After controlling for confounding variables, the following risk factors were associated with ASB in patients with T2DM: age (WMD = 3.18, 95% CI (1.91, 4.45), I2 = 75.5%, P < 0.001), female sex (OR = 1.07, 95% CI(1.02, 1.12), I2 = 79.3%, P = 0.002), duration of type 2 diabetes (WMD = 2.54, 95% CI (1.53, 5.43), I2 = 80.7%, P < 0.001), HbA1c (WMD = 0.63, 95% CI (0.43, 0.84), I2 = 62.6,%. P < 0.001), hypertension (OR = 1.59, 95% CI (1.24, 2.04), I2 = 0%, <0.001), hyperlipidemia (OR = 1.66, 95% CI (1.27, 2.18), I2 = 0%, P < 0.001), Neuropathy (OR = 1.81, 95% CI (1.38, 2.37), I2 = 0%, P < 0.001), proteinuria (OR = 3.00, 95% CI (1.82, 4.95), I2 = 62.7%, P < 0.001).ConclusionThe overall prevalence of ASB in T2DM is 23.7%. Age, female sex, course of T2DM, HbA1C, hypertension, hyperlipidemia, neuropathy, and proteinuria were identified as related risk factors for ASB in T2DM. These findings can provide a robust theoretical basis for preventing and managing ASB in T2DM.

Urinary tract infections in patients with diabetes

Differential diagnosis of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is based on the presence of diverse symptoms, including fever (≥38.5°C), rigors, malaise, lethargy, flank pain, hematuria, suprapubic discomfort, dysuria, and urgent or frequent urination. There is consensus in the medical community that ASB warrants antibiotic treatment only for patients undergoing urological procedures that lead to mucosal bleeding, catheterized individuals whose ASB persists for more than 48 h after catheter removal, and pregnant women. Pyuria is associated with UTI and implicates host immune responses via release of antibacterial effectors and phagocytosis of pathogens by neutrophils. Such responses are not sufficiently described for ASB. Metaproteomic methods were used here to identify the pathogens and evaluate molecular evidence of distinct immune responses in cases of ASB compared to UTI in elderly patients who were hospitalized upon injury. Neutrophil-driven inflammatory responses to invading bacteria were not discernible in most patients diagnosed with ASB compared to those with UTI. In contrast, proteomic urine analysis for trauma patients with no evidence of bacteriuria, including those who suffered mucosal injuries via urethral catheterization, rarely showed evidence of neutrophil infiltration. The same enzymes contributing to the synthesis of leukotrienes LTB4 and LTC4, mediators of inflammation and pain, were found in the UTI and ASB cohorts. These data support the notion that the pathways mediating inflammation and pain in most elderly patients with ASB are not quantitatively different from those seen in most elderly patients with UTI and warrant larger clinical studies to assess whether a common antibiotic treatment strategy for elderly ASB and UTI patients is justified.

Escherichia coli can colonise the urogenital tract of individuals without causing symptoms of infection, in a condition referred to as asymptomatic bacteriuria (ABU). ABU isolates can protect the host against symptomatic urinary tract infections (UTIs) by bacterial interference against uropathogenic E. coli (UPEC). The aim of this study was to investigate the genotypic and phenotypic characteristics of five ABU isolates from midstream urine samples of adults. Comparative genomic and phenotypic analysis was conducted including an antibiotic resistance profile, pangenome analysis, and a putative virulence profile. Based on the genome analysis, the isolates consisted of one from phylogroup A, three from phylogroup B2, and one from phylogroup D. Two of the isolates, PUTS 58 and SK-106-1, were noted for their lack of antibiotic resistance and virulence genes compared to the prototypic ABU strain E. coli 83,972. This study provides insights into the genotypic and phenotypic profiles of uncharacterised ABU isolates, and how relevant fitness and virulence traits can impact their potential suitability for therapeutic bacterial interference.

Extra-intestinal pathogenic Escherichia coli (ExPEC) causing urinary tract infections (UTIs) most often belong to phylogenetic group B2 and stem from the patient's own faecal flora. It has been hypothesized that the external reservoir for these uropathogenic E. coli in the human intestine may be meat and food-production animals. To investigate such a connection, this study analysed an E. coli phylogroup B2 strain collection (n = 161) of geographical and temporally matched isolates, published previously, from UTI patients (n = 52), community-dwelling humans (n = 36), imported (n = 5) and Danish (n = 13) broiler chicken meat, Danish broiler chickens (n = 17), imported (n = 3) and Danish (n = 27) pork, and healthy Danish pigs (n = 8). The isolates were subjected to microarray analysis for 315 virulence genes and variants and 82 antimicrobial resistance genes and variants. In total, 133 different virulence and antimicrobial resistance genes were detected in at least one UTI isolate. Between 66 and 87 of these genes were also detected in meat and animal isolates. Cluster analyses of virulence and resistance gene profiles, respectively, showed that UTI and community-dwelling human isolates most often grouped with meat and animal isolates, indicating genotypic similarity among such isolates. Furthermore, B2 isolates were detected from UTI patients and meat, with indistinguishable gene profiles. A considerable proportion of the animal and meat isolates belonged to the ExPEC pathotype. In conclusion, these findings suggest that B2 E. coli from meat and animal origin can be the source of most of the virulence and antimicrobial resistance genes detected in uropathogenic E. coli isolates and that there is a general resemblance of animal, meat and UTI E. coli based on extended gene profiling. These findings support the hypothesis of a zoonotic link between E. coli causing UTIs and E. coli from meat and animals.

Antimicrobial Prophylaxis for Postoperative Urinary Tract Infections in Transurethral Resection of Bladder Tumors: A Systematic Review and Meta-Analysis.

ABSTRACTObjective:To estimate the efficacy of antibiotic prophylaxis to prevent urinary tract infection in patients (both gender) who undergo a cystoscopy with sterile urine.Materials and Methods:Search strategy (January 1980-December 2013) in Medline via PubMed, CENTRAL, and EMBASE. Additionally, we searched databases for registered trials and conference abstracts, as well as reference lists of systematic reviews and included studies. Seven published randomized clinical trials (January 1, 1980 to December 31, 2013) were included in quantitative analyses with no language restrictions. Two independent reviewers collected data. Risk of bias was evaluated with the Cochrane Collaboration tool. We performed a fixed effect analyses due to statistical homogeneity. The primary outcome was urinary tract infection and the secondary was asymptomatic bacteriuria. The effect measure was the risk difference (RD) with 95% confidence interval. The planned interventions were: Antibiotic vs placebo; Antibiotic vs no intervention and Antibiotic vs any other intervention.Results:3038 patients were found in seven studies. For the primary outcome, we included 5 studies and we found a RR 0.53 CI95% (0.31, 0.90) and a RD-0.012 CI95% (-0.023,-0.002), favoring antibiotic prophylaxis. For asymptomatic bacteriuria we included 6 studies and we found a RR 0.28 CI95% (0.20, 0.39) and a RD-0.055 CI95% (-0.07,-0.039), was found favoring prophylaxis. According to GRADE evaluation, we considered moderate quality of evidence for both outcomes. The subgroup analysis showed that only two studies were classified as having low risk of bias: Cam 2009 and García-Perdomo 2013. They showed no statistical differences (RD-0.009 CI95% -0.03, 0.011).Conclusions:Based on studies classified as low risk of bias, we found moderate evidence to not recommend the use of antibiotic prophylaxis to prevent urinary tract infection and asymptomatic bacteriuria in patients who undergo cystoscopy with sterile urine in an ambulatory setting.

BACKGROUND: High prevalence of asymptomatic bacteriuria (ASB) was reported in dialysis patients. Meanwhile, chronic inflammation, including chronic infection, was widely proved to be one of the most important risk factors of morbidity and mortality in maintenance hemodialysis (HD) patients. The aim of this study was to clarify the clinical implications of ASB in long-term HD patients via analyzing its epidemiology, microbiology, relationship with pyuria, predisposing factors and impact on inflammatory state.METHODS: Forty-two patients on stable long-term HD without symptoms of urinary tract infection (UTI) were included in this study. Two specimens of clean-catch urine were collected separately for general analysis and bacterial culture. Baseline characteristics, hemogram, biochemical parameters and inflammatory markers, albumin and C-reactive protein (CRP), between patients with ASB (＞ 1×10^5 colony-forming units per mL of a single microorganism) and without ASB were compared, Moreover, in view of the close association between ASB and pyuria (＞ 10 white cell count per high-power field), the prevalence, predisposing factors, predictability of ASB and chronic inflammatory activity of patients with pyuria were also examined.RESULTS: Twenty-nine percent (12 in 42) of HD patients had significant single bacteriuria. E. coli was the most common bacterium. All of the patients with ASB also had pyuria. The prevalence rate of ASB was markedly associated with old age (P=0.008) and diabetes (P=0.001). Comparison between patients with and without ASB showed no difference in albumin and CRP level. Moreover, 50 % (21 in 42) of patients revealed positive pyuria results. Among the 21 patients, 12 (57%) indicated ASB. The predisposing factors included decreased daily urine amount (P=0.006) and diabetes (P=0.005). As in ASB, no difference in inflammatory markers was found when comparing between patients with and without pyuira.CONCLUSION: In chronic HD patients, ASB was common and pyuria was a good predictor. The major risk factors were old age and diabetes. Even though patients with ASB or pyuria revealed a trend toward worse inflammatory state, the difference showed no statistical significance.

Urinary tract infections in patients with diabetes mellitus: epidemiology, pathogenesis and treatment

Whole-genome comparison of urinary pathogenic Escherichia coli and faecal isolates of UTI patients and healthy controls