Urinary Tract Infection Susceptibility Research Articles

Insulin receptor orchestrates kidney antibacterial defenses

Urinary tract infection (UTI) commonly afflicts people with diabetes. This augmented infection risk is partly due to deregulated insulin receptor (IR) signaling in the kidney collecting duct. The collecting duct is composed of intercalated cells (ICs) and principal cells (PCs). Evidence suggests that ICs contribute to UTI defenses. Here, we interrogate how IR deletion in ICs impacts antibacterial defenses against uropathogenic Escherichia coli. We also explore how IR deletion affects immune responses in neighboring PCs with intact IR expression. To accomplish this objective, we profile the transcriptomes of IC and PC populations enriched from kidneys of wild-type and IC-specific IR knock-out mice that have increased UTI susceptibility. Transcriptomic analysis demonstrates that IR deletion suppresses IC-integrated stress responses and innate immune defenses. To define how IR shapes these immune defenses, we employ murine and human kidney cultures. When challenged with bacteria, murine ICs and human kidney cells with deregulated IR signaling cannot engage central components of the integrated stress response-including activating transcriptional factor 4 (ATF4). Silencing ATF4 impairs NFkB activation and promotes infection. In turn, NFkB silencing augments infection and suppresses antimicrobial peptide expression. In diabetic mice and people with diabetes, collecting duct cells show reduced IR expression, impaired integrated stress response engagement, and compromised immunity. Collectively, these translational data illustrate how IR orchestrates collecting duct antibacterial responses and the communication between ICs and PCs.

Prevalence and Antibiotic Susceptibility of Urinary Tract Infections in Diabetic and Non Diabetic Individuals: A Prospective Study

Background & Objectives: Diabetes mellitus is increasingly recognized as a major health concern worldwide, particularly in developing countries like India. Diabetic individuals are known to have a higher susceptibility to urinary tract infections (UTIs), compounded by the emergence of drug-resistant uropathogens. This study aims to determine the prevalence and etiology of UTIs in diabetic patients. Materials and Methods: A cross-sectional prospective study involving 220 individuals was conducted from March to April 2023 to assess the spectrum of pathogens causing UTIs and their antibiotic susceptibility. Primary cultures were performed on McConkey agar and sheep blood agar, followed by identification and antimicrobial susceptibility testing (AST) using the Vitek2 system and Kirby Bauer's disc diffusion method on Mueller-Hinton agar. Results: Of the 220 samples tested, 150 exhibited significant bacteriuria, with 36 (75%) of 48 diabetic individuals testing positive for UTIs. Gram-negative bacilli (GNB) accounted for 135 (61.4%) isolates, with Escherichia coli (E. coli) being the most prevalent pathogen (52.7%), followed by Klebsiella spp. (25.3%). Among gram-positive organisms, Enterococcus spp. (5.3%) were predominant, with Candida isolates detected in 3 cases (2%). Meropenem (87.6%) exhibited the highest susceptibility against GNB, followed by Netilmycin (87.6%) and Imipenem (82.5%). For gram-positive organisms, Imipenem and Nitrofurantoin demonstrated high susceptibility. Conclusion: E. coli emerged as the predominant pathogen in both diabetic and non-diabetic populations. High sensitivity to meropenem, imipenem, amikacin, and fosfomycin was observed in both groups, suggesting their potential for empirical treatment. Regular surveillance of drug resistance patterns is crucial for identifying evolving resistance trends and optimizing treatment strategies.

DEFA1A3 DNA gene-dosage regulates the kidney innate immune response during upper urinary tract infection.

Antimicrobial peptides (AMPs) are host defense effectors with potent neutralizing and immunomodulatory functions against invasive pathogens. The AMPs α-Defensin 1-3/DEFA1A3 participate in innate immune responses and influence patient outcomes in various diseases. DNA copy-number variations in DEFA1A3 have been associated with severity and outcomes in infectious diseases including urinary tract infections (UTIs). Specifically, children with lower DNA copy numbers were more susceptible to UTIs. The mechanism of action by which α-Defensin 1-3/DEFA1A3 copy-number variations lead to UTI susceptibility remains to be explored. In this study, we use a previously characterized transgenic knock-in of the human DEFA1A3 gene mouse to dissect α-Defensin 1-3 gene dose-dependent antimicrobial and immunomodulatory roles during uropathogenic Escherichia coli (UPEC) UTI. We elucidate the relationship between kidney neutrophil- and collecting duct intercalated cell-derived α-Defensin 1-3/DEFA1A3 expression and UTI. We further describe cooperative effects between α-Defensin 1-3 and other AMPs that potentiate the neutralizing activity against UPEC. Cumulatively, we demonstrate that DEFA1A3 directly protects against UPEC meanwhile impacting pro-inflammatory innate immune responses in a gene dosage-dependent manner.

Prevalence and Susceptibility of Urinary Tract Infections’ Bacteria in Catheterized Patients to Commonly Used Antibiotics

Prevalence and Susceptibility of Urinary Tract Infections’ Bacteria in Catheterized Patients to Commonly Used Antibiotics

Androgen exposure impairs neutrophil maturation and function within the infected kidney.

Urinary tract infections (UTIs) in men are uncommon yet carry an increased risk for severe pyelonephritis and other complications. In models of Escherichia coli UTI, C3H/HeN mice develop high-titer pyelonephritis (most with renal abscesses) in a testosterone-dependent manner, but the mechanisms underlying this phenotype are unknown. Here, using female mouse models, we show that androgen exposure impairs neutrophil maturation in the upper and lower urinary tract, compounded by a reduction of neutrophil function within the infected kidney, enabling persistent high-titer infection and promoting abscess formation. Following intravesical inoculation with uropathogenic E. coli (UPEC), kidneys of androgen-exposed C3H mice showed delayed local pro-inflammatory cytokine responses while robustly recruiting neutrophils. These were enriched for an end-organ-specific population of aged but immature neutrophils (CD49d+, CD101-). Compared to their mature counterparts, these aged immature kidney neutrophils exhibited reduced function in vitro, including impaired degranulation and diminished phagocytic activity, while splenic, bone marrow, and bladder neutrophils did not display these alterations. Furthermore, aged immature neutrophils manifested little phagocytic activity within intratubular UPEC communities in vivo. Experiments with B6 conditional androgen receptor (AR)-deficient mice indicated rescue of the maturation defect when AR was deleted in myeloid cells. We conclude that the recognized enhancement of UTI severity by androgens is attributable, at least in part, to local impairment of neutrophil maturation in the urinary tract (largely via cell-intrinsic AR signaling) and a kidney-specific reduction in neutrophil antimicrobial capacity.IMPORTANCEAlthough urinary tract infections (UTIs) predominantly occur in women, male UTIs carry an increased risk of morbidity and mortality. Pyelonephritis in androgen-exposed mice features robust neutrophil recruitment and abscess formation, while bacterial load remains consistently high. Here, we demonstrate that during UTI, neutrophils infiltrating the urinary tract of androgen-exposed mice exhibit reduced maturation, and those that have infiltrated the kidney have reduced phagocytic and degranulation functions, limiting their ability to effectively control infection. This work helps to elucidate mechanisms by which androgens enhance UTI susceptibility and severity, illuminating why male patients may be predisposed to severe outcomes of pyelonephritis.

Murine Ribonuclease 6 Limits Bacterial Dissemination during Experimental Urinary Tract Infection.

The ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTIs). In this study, we generated Rnase6-deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI. We generated a Rnase6EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility. We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6EGFP/+ mice. Rnase6 deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+ controls. UPEC displayed increased intracellular survival in Rnase6-deficient macrophages. Our findings establish that RNase6 prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.

Bacterial aetiology, antimicrobial susceptibility patterns, and factors associated with urinary tract infection among under-five children at primary health facility, North-Western Tanzania.

Urinary tract infections (UTI) are common in under-five children, with significant consequences leading to bacteremia, dehydration, kidney scarring, and renal failure. The incidence of UTI varies with patients' demographics and geographic location. Limited studies have addressed UTI issues, particularly in children. We determined the proportion of UTI, bacterial aetiology, and antimicrobial susceptibility patterns and associated factors among under-five children at the district hospital between March and April 2023. We conducted a cross-sectional study using a convenient non-probability sampling technique to collect urine samples from participants with signs and symptoms of UTI. Written informed consent was obtained from parents or guardians. We collected Participants' information using a pretested structured questionnaire. Urine samples were processed at the Regional Referral Hospital. All analyses were conducted using STATA version 15.0. We determined the factors associated with UTI using a modified Poisson model multivariable analysis of the modified Poisson model. The results were presented as a prevalence ratio and 95% confidence interval. The level of significance was specified at 0.05. The study recruited 368 under-five children; 194 (52.7%) were males, and the median age (interquartile range) was 24 (13-36) months. Of all, 28.8% (95% CI-24.3-33.6) had culture-confirmed UTI. One hundred and six pathogens were isolated, the majority being Escherichia coli (E. coli), 37 (34.9%), and Staphylococcus aureus (S. aureus), 26 (24.5%). The susceptibility of E. coli to cefepime, piperacillin-tazobactam, nitrofurantoin, and meropenem ranged from 81.1% to 97.3%. S. aureus was most susceptible to nitrofurantoin (96.2%) and ciprofloxacin (92.3%). Multidrug resistance was observed in 33.0% of isolates. The proportion of Methicillin-resistant S. aureus and extended-spectrum beta-lactamases was 23.1% and 25%, respectively. UTI was observed more in patients presenting with vomiting, dysuria, and abdominal pain, patients below 24 months of age, nappy users, and uncircumcised males. Our study found a relatively high proportion of UTI among under-five children associated with vomiting, dysuria, abdominal pain, nappy use, and uncircumcision in males. The pathogens were least susceptible to (trimethoprim-sulfamethoxazole, gentamycin, ampicillin, and penicillin) the commonly used antibiotic. We advocate a thorough clinical analysis to detect the predictors of UTI and a periodic review of empirical treatment of UTI based on the antibiotic susceptibility pattern.

Beyond the urothelium: Interplay between autonomic nervous system and bladder inflammation in urinary tract infection, bladder pain syndrome with interstitial cystitis and neurogenic lower urinary tract dysfunction in spinal cord injury-ICI-RS 2023.

Inflammation and neuronal hypersensitivity are reactive protective mechanisms after urothelial injury. In lower urinary tract dysfunctions (LUTD), such as urinary tract infection (UTI), bladder pain syndrome with interstitial cystitis (BPS/IC) and neurogenic LUTD after spinal cord injury (SCI), chronic inflammation can develop. It is unclear how the protective reactionary inflammation escalates into chronic disease in some patients. During its 2023 meeting in Bristol, the International Consultation on Incontinence-Research Society (ICI-RS) reviewed the urothelial and inflammatory changes after UTI, BPS/IC and SCI. Potential factors contributing to the evolution into chronic disease were explored in a think-tank. Five topics were discussed. (1) Visceral fat metabolism participates in the systemic pro-inflammatory effect of noradrenalin in BPS/IC and SCI. Sympathetic nervous system-adipocyte-bladder crosstalk needs further investigation. (2) Sympathetic hyperactivity also potentiates immune depression in SCI and needs to be investigated in BPS/IC. Gabapentin and tumor necrosis factor-α are promising research targets. (3) The exact peripheral neurons involved in the integrative protective unit formed by nervous and immune systems need to be further identified. (4) Neurotransmitter changes in SCI and BPS/IC: Neurotransmitter crosstalk needs to be considered in identifying new therapeutic targets. (5) The change from eubiosis to dysbiosis in SCI can contribute to UTI susceptibility and needs to be unraveled. The think-tank discussed whether visceral fat metabolism, immune depression through sympathetic hyperactivity, peripheral nerves and neurotransmitter crosstalk, and the change in microbiome could provide explanations in the heterogenic development of chronic inflammation in LUTD. High-priority research questions were identified.

Establishment of Baseline Urinary Antimicrobial Peptide Levels by Age: A Prospective Observational Study.

Antimicrobial peptides (AMPs) are key effectors of urinary tract innate immunity. Identifying differences in urinary AMP levels between younger and older adults is important in understanding older adults' susceptibility and response to urinary tract infections (UTI) and AMP use as diagnostic biomarkers. We hypothesized that uninfected older adults have higher urinary human neutrophil peptides 1-3 (HNP 1-3), human alpha-defensin-5 (HD-5), and human beta-defensin-2 (hBD-2), but lower urinary cathelicidin (LL-37) than younger adults. We conducted a cross-sectional study of patients aged ≥18 years completing a family medicine clinic nonacute visit. Enzyme-linked immunosorbent assays were performed for AMPs. We identified associations between age and AMPs using unadjusted and multivariable linear regression models. Of the 308 subjects, 144 (46.8%) were ≥65 years of age. Comparing age ≥65 versus < 65 years, there were no significant differences in HNP 1-3 (p = .371), HD5 (p = .834), or LL-37 (p = .348) levels. Values for hBD-2 were lower in older adults versus younger (p < .001). In multivariable analyses, older males and females had significantly lower hBD-2 levels (p < .001 and p = .004). Models also showed urine leukocyte esterase was associated with increased levels of HNP 1-3 and HD5; hematuria with increased hBD-2; and urine cultures with contamination with increased HNP 1-3 and hBD-2. Baseline urinary HNP 1-3, HD-5, and LL-37 did not vary with age. Older adults had lower baseline hBD-2. This finding has implications for the potential use of urinary AMPs as diagnostic markers and will facilitate further investigation into the role of innate immunity in UTI susceptibility in older adults.

Indwelling catheter vs intermittent catheterization: is there a difference in UTI susceptibility?

BackgroundPatients with neurogenic lower urinary tract dysfunction (NLUTD) often rely on some type of catheterization for bladder emptying. Intermittent catheterization (IC) is considered the gold standard and is preferred over continuous catheterization, since it is considered to cause fewer urinary tract infections (UTIs) than indwelling catheterization. The main objective of our study was to describe UTI prevalence (at visit) and incidence (within the last 12 months) and urine culture characteristics between patients using an indwelling catheter versus (vs) those performing IC.MethodsIn this cross-sectional study, we prospectively evaluated from 02/2020 to 01/2021 patients with NLUTD undergoing urine cultures for prophylactic reasons or due to UTI symptoms. At visit, all patients underwent a standardized interview on current UTI symptoms as well as UTI history and antibiotic consumption within the past year. Patients using an indwelling catheter (n = 206) or IC (n = 299) were included in the analysis. The main outcome was between-group differences regarding UTI characteristics.ResultsPatients using an indwelling catheter were older (indwelling catheter vs IC: median 66 (Q1-Q3: 55—77) vs 55 (42—67) years of age) and showed a higher Charlson comorbidity index (indwelling catheter vs IC: median 4 (Q1-Q3: 2–6) vs 2 (1–4) (both p < 0·001).A total of 40 patients from both groups were diagnosed with a UTI at visit (indwelling catheters vs IC: 8% (16/206) vs 8% (24/299); p = 0·782), and the number of UTIs within the past 12 months was not significantly different between groups. Overall, Escherichia coli (21%), Enterococcus faecalis (17%), and Klebsiella spp. (12%) were the most frequently detected bacteria.ConclusionsIn this cohort of patients with NLUTD, we did not find relevant differences in UTI frequency between groups. These results suggest that UTI-related concerns should not be given undue emphasis when counseling patients for catheter-related bladder emptying methods.

Prevalence, Risk Factors and Antibiotic Susceptibility of Urinary Tract Infections among Pregnant Women: A Study in Damt District Yemen

Urinary tract infections are the most common illnesses that impact pregnant women. This study aimed to investigate bacterial urinary tract infections and antibiotic susceptibility profiles in pregnant women. This study was conducted on pregnant women between April and October 2021 in clinics and hospitals in the Damt district. Midstream urine samples were collected, cultured, identified and tested for antibiotic susceptibility. The prevalence of UTI in pregnant women was 210/350 (60%). Escherichia coli accounted for 90/210 (42.9%), Staphylococcus aureus 50/210 (23.8%), and Klebsiella pneumoniae 25/210 (11.9%). Staphylococcus epidermidis, Pseudomonas aeruginosa, and Proteus mirabilis exhibited 15/210 (7.1%) of each with the moderately identified bacterial species. Antimicrobial sensitivity testing showed that bacterial isolates were resistant to amoxicillin (80-100%), ceftriaxone (40-70%), gentamycin (0-60%), amikacin (0-50%), tetracycline, ciprofloxacin, azithromycin, and amoxiclav (0-40%), and azithromycin (0-30%). Significant bacteriuria was associated with age (p = 0.01), pregnancy trimesters (p = 0.00), gestation (p = 0.00), and residence (p = 0.03), whereas there was no association with education (p = 0.05). Most isolates have become resistant toward antibiotic used in the study treatments, especially ceftriaxone and amoxicillin. Therefore, it is recommended that pregnant women undergo health education on the prevalence and causes of urinary tract infections.

Causal relationship between type 1 diabetes mellitus and six high-frequency infectious diseases: A two-sample mendelian randomization study.

Type 1 diabetes mellitus (T1DM) is associated with different types of infections; however, studies on the causal relationship between T1DM and infectious diseases are lacking. Therefore, our study aimed to explore the causalities between T1DM and six high-frequency infections using a Mendelian randomization (MR) approach. Two-sample MR studies were conducted to explore the causalities between T1DM and six high-frequency infections: sepsis, acute lower respiratory infections (ALRIs), intestinal infections (IIs), infections of the genitourinary tract (GUTIs) in pregnancy, infections of the skin and subcutaneous tissues (SSTIs), and urinary tract infections (UTIs). Data on summary statistics for T1DM and infections were obtained from the European Bioinformatics Institute database, the United Kingdom Biobank, FinnGen biobank, and Medical Research Council Integrative Epidemiology Unit. All data obtained for summary statistics were from European countries. The inverse-variance weighted (IVW) method was employed as the main analysis. Considering the multiple comparisons, statistical significance was set at p< 0.008. If univariate MR analyses found a significant causal association, multivariable MR (MVMR) analyses were performed to adjust body mass index (BMI) and glycated hemoglobin (HbA1c). MVMR-IVW was performed as the primary analysis, and the least absolute shrinkage and selection operator (LASSO) regression and MVMR-Robust were performed as complementary analyses. MR analysis showed that susceptibility to IIs increased in patients with T1DM by 6.09% using the IVW-fixed method [odds ratio (OR)=1.0609; 95% confidence interval (CI): 1.0281-1.0947, p=0.0002]. Results were still significant after multiple testing. Sensitivity analyses did not show any significant horizontal pleiotropy or heterogeneity. After adjusting for BMI and HbA1c, MVMR-IVW (OR=1.0942; 95% CI: 1.0666-1.1224, p<0.0001) showed significant outcomes that were consistent with those of LASSO regression and MVMR-Robust. However, no significant causal relationship was found between T1DM and sepsis susceptibility, ALRI susceptibility, GUTI susceptibility in pregnancy, SSTI susceptibility, and UTI susceptibility. Our MR analysis genetically predicted increased susceptibility to IIs in T1DM. However, no causality between T1DM and sepsis, ALRIs, GUTIs in pregnancy, SSTIs, or UTIs was found. Larger epidemiological and metagenomic studies are required to further investigate the observed associations between the susceptibility of certain infectious diseases with T1DM.

Effects of aging on urinary tract epithelial homeostasis and immunity

A global increase in older individuals creates an increasing demand to understand numerous healthcare challenges related to aging. This population is subject to changes in tissue physiology and the immune response network. Older individuals are particularly susceptible to infectious diseases, with one of the most common being urinary tract infections (UTIs). Postmenopausal and older women have the highest risk of recurrent UTIs (rUTIs); however, why rUTIs become more frequent after menopause and during old age is incompletely understood. This increased susceptibility and severity among older individuals may involve functional changes to the immune system with age. Aging also has substantial effects on the epithelium and the immune system that led to impaired protection against pathogens, yet heightened and prolonged inflammation. How the immune system and its responses to infection changes within the bladder mucosa during aging has largely remained poorly understood. In this review, we highlight our understanding of bladder innate and adaptive immunity and the impact of aging and hormones and hormone therapy on bladder epithelial homeostasis and immunity. In particular, we elaborate on how the cellular and molecular immune landscape within the bladder can be altered during aging as aged mice develop bladder tertiary lymphoid tissues (bTLT), which are absent in young mice leading to profound age-associated change to the immune landscape in bladders that might drive the significant increase in UTI susceptibility. Knowledge of host factors that prevent or promote infection can lead to targeted treatment and prevention regimens. This review also identifies unique host factors to consider in the older, female host for improving rUTI treatment and prevention by dissecting the age-associated alteration of the bladder mucosal immune system.

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

BackgroundThe 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). ObjectiveTo 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 participantsBlood 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 analysisTLR 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 limitationsUrine 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. ConclusionsAntibiotic 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 summaryOur 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.

URINARY TRACT INFECTION IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA ADMITTED FOR PROSTATECTOMY

&nbsp; &nbsp;Urinary Tract Infection (UTI) in patients with Benign Prostatic Hyperplasia (BPH) causes UTI related complication before and after prostatectomy, reduction in their health-related quality of life and overall well-being, thus the knowledge of UTI may play a complementary role in management.The aim of this research was to study the prevalence of urinary tract infection (UTI), its causative organism and antibiotic susceptibility. All BPH patients who were admitted for prostatectomy were included to the study. Information on age, presence of an indwelling catheter, other factors related to UTI and antibiotic susceptibility results were obtained and analyzed using IBM SPSS version 26. Three hundred twenty six patients were studied. The age range of study participants was 51 to 89 years and displayed a median of 70 year (IQR=12). More than half of study participants 168 (51.5%) were between 61 to 70 years. Bacterial isolates were noted in 96 (29.4%) patients. Escherichia Coli noted in (25.3%) specimens was the most common organism isolated. The bacterial isolates were mostly sensitive to imipenem, meropenem, and fosfomycin, but showed greater resistance to cefotaxime, ceftazideme and cefazulin accordingly. The age of study participants was significantly greater for those who had bacteriuria (Mdn = 70) years than those who did not have bacteriuria (Mdn = 67), U = 9569, P = 0.048. The same it was significant for PSA level (P = 0.000) but were not significant for prostate size (P = 0.558). Less than one third of BPH patients had UTI (29.4%), E. Coli was the most common microbial cause of UTI in study participants it was the cause in one fourth of cases (25%), Imipenem group of antibiotic was the most sensitive antibiotics in study participants (93.9%), Cefotaxime was the most resistant antibiotics (66.7%)

Ribonuclease 7 polymorphism rs1263872 reduces antimicrobial activity and associates with pediatric urinary tract infections.

Ribonuclease 7 (RNase 7) is an antimicrobial peptide that prevents urinary tract infections (UTI); however, it is yet unknown how RNASE7 genetic variations affect its antimicrobial activity and its mitigation of UTI risk. This study determined whether the RNASE7 SNP rs1263872 is more prevalent in children with UTI and defined how rs1263872 affects RNase 7's antimicrobial activity against uropathogenic E. coli (UPEC). We performed genotyping for rs1263872 in 2 national UTI cohorts, including children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux trial or the Careful Urinary Tract Infection Evaluation study. Genotypes from these cohorts were compared with those of female controls with no UTI. To assess whether rs1263872 affects RNase 7's antimicrobial activity, we generated RNase 7 peptides and genetically modified urothelial cultures encoding wild-type RNase 7 and its variant. Compared with controls, girls in both UTI cohorts had an increased prevalence of the RNASE7 variant. Compared with the missense variant, wild-type RNase 7 peptide showed greater bactericidal activity against UPEC. Wild-type RNase 7 overexpression in human urothelial cultures reduced UPEC invasive infection compared with mutant overexpression. These results show that children with UTI have an increased prevalence of RNASE7 rs1263872, which may increase UTI susceptibility by suppressing RNase 7's antibacterial activity.

Longitudinal Follow-Up of Urinary Tract Infections and Their Treatment in Mice using Bioluminescence Imaging.

Urinary tract infections (UTI) rank among the most common bacterial infections in humans and are routinely treated with empirical antibiotics. However, due to increasing microbial resistance, the efficacy of the most used antibiotics has declined. To find alternative treatment options, there is a great need for a better understanding of the UTI pathogenesis and the mechanisms that determine UTI susceptibility. In order to investigate this in an animal model, a reproducible, non-invasive assay to study the course of UTI is indispensable. For years, the gold standard for the enumeration of bacterial load has been the determination of Colony Forming Units (CFU) for a particular sample volume. This technique requires post-mortem organ homogenates and serial dilutions, limiting data output and reproducibility. As an alternative, bioluminescence imaging (BLI) is gaining popularity to determine the bacterial load. Labeling pathogens with a lux operon allow for the sensitive detection and quantification in a non-invasive manner, thereby enabling longitudinal follow-up. So far, the adoption of BLI in UTI research remains limited. This manuscript describes the practical implementation of BLI in a mouse urinary tract infection model. Here, a step-by-step guide for culturing bacteria, intravesical instillation and imaging is provided. The in vivo correlation with CFU is examined and a proof-of-concept is provided by comparing the bacterial load of untreated infected animals with antibiotic-treated animals. Furthermore, the advantages, limitations, and considerations specific to the implementation of BLI in an in vivo UTI model are discussed. The implementation of BLI in the UTI research field will greatly facilitate research on the pathogenesis of UTI and the discovery of new ways to prevent and treat UTI.

Validation of point-of-care device for rapid detection of urinary tract infection and antibiotic susceptibility

Urinary tract infections (UTI) presents a high prevalence in the community setting. Rapid and accurate microbiological diagnosis is essential to ensure adequate and effective therapy. To evaluate a rapid antibiogram kit (KAR®) in point-of-care format for rapid detection of UTI and antibiotic susceptibility. The KAR® device has been designed and developed in collaboration with technical engineers and clinical microbiologists. Its evaluation has been carried out through a multicenter study in which three Spanish hospitals have participated. Thus, different in vivo tests have been implemented in order to determine device correlation with the reference microbiological techniques. During the study period, a total of 400 urine samples from patients with suspected ITU were tested. The KAR® device provided fast results (mean positivity time of 7,8 ± 1,5 hours) with 97% sensitivity, 89% specificity and 87% agreement for the detection of significant bacteriuria. The percentages of specificity for the antibiotics tested were: ciprofloxacin (97%), fosfomycin (94%),cotrimoxazole (84%), ampicillin (80%) and amoxicillin/clavulanic acid (55%). The KAR® device could be a useful tool for diagnosing UTI in outpatients, especially in areas of low socio-economic level.

Effects of Dapagliflozin-Induced Glucosuria on Urinary Tract Infection Susceptibility

Effects of Dapagliflozin-Induced Glucosuria on Urinary Tract Infection Susceptibility

P0285A COMPARISON OF URINE MICROSCOPY AND CULTURE IN HIV-INFECTED AND NON HIV-INFECTED INDIVIDUALS IN THE ANTI-RETROVIRAL ERA

Abstract Background and Aims Urinary tract infection is among the most common causes of sepsis presenting in hospitals. The aim was to collect data to enable empirical treatment of urinary tract infections in HIV negative and positive nephrology patients while waiting for urine culture results in order to reduce hospital stay. Our aim is also to assess incidence and antimicrobial susceptibility of urinary tract infections in HIV negative and positive patients. Method A retrospective chart review of nephrology patients admitted from January to December 2014 in Nephrology ward and the first consecutive 200 outpatients seen in Nephrology clinic in 2014 at Inkosi Albert Luthuli Central Hospital was conducted. Information was gathered with the use of a data collection sheet and urinary tract infection was based on urine culture results. All data was analysed using Statistical Package for Social Sciences version 23. Percentages of basic characteristics were calculated between groups. Logistic regression analysis was used to identify factors associated with positive urine culture. Results There were 654 patients in the study, 514 (79%) were HIV negative and 139 (21%) were HIV positive. The incidence of UTI in nephrology patients was 9%, 10.1% in inpatients and 6.5% in outpatients. 22% were HIV positive (p value 0.883, 95% CI 0.550-2.003). 19% had Diabetes mellitus, 15% had Systemic Lupus Erythematosus and 5% were post renal transplant patients. Escherichia coli and Klebsiella pneumonia were the common causes of urinary tract infection at 40.7% and 15.3% respectively with 22% cases on extended beta lactam resistance. Conclusion There was no statistically significant difference on the incidence and anti-microbial isolates between HIV infected and HIV negative nephrology patients with urinary tract infection. Hence, empirical treatment for UTI should remain the same in the 2 groups. Escherichia coli and Klebsiella pneumoniae were the most commonly cultured organisms in both groups. There is microbial resistance to commonly used antibiotics. Constant assessment of anti-microbial sensitivity of urinary tract infections is of paramount importance.