Evaluation of antibacterial, antifungal and antibiofilm activities of A. baumannii-derived tannase and gallic acid against uropathogenic microorganisms.

One of the most prevalent infectious diseases and a key driver of antibiotic prescriptions in pediatrics is urinary tract infection (UTI). Due to the emergence of more resistant uropathogenic bacterial and fungal strains, current treatments are no longer effective, necessitating the urgent development of novel antibacterial and antifungal drugs. In this study, the antifungal, antibacterial, and anti-biofilm capabilities of compounds, such as tannase (TN) and gallic acid (GA), which were produced from a novel natural source, Acinetobacter baumannii (AB11) bacteria, were assessed for the inactivation of uropathogenic microorganisms (UMs). Ammonium sulphate precipitation, ion exchange, high-performance liquid chromatography, and gel filtration were used to purify TN and GA that were isolated from A. baumannii. A 43.08 % pure TN with 1221.2 U/mg specific activity and 10.51 mg/mL GA was obtained. The antibacterial, antifungal and anti-biofilm activities of TN and GA were evaluated against UMs and compared to those of commercially available antibiotics including sulfamethoxazole (SXT), levofloxacin (LEV), ciprofloxacin (CIP), amikacin (Ak), and nitrofurantoin (F). The results showed that TN and GA were superior to commercial antibiotics in their ability to inactivate UMs and considerably reduced biofilms formation. Additionally, the GA emerges as the top substitute for currently available medications, demonstrating superior antibacterial and antibiofilm properties against all UMs evaluated in this study. The results of this investigation showed that A. baumannii-derived TN and GA could be utilized as an alternative medication to treat UTIs.

Two novel phages, Klebsiella phage GADU21 and Escherichia phage GADU22, from the urine samples of patients with urinary tract infection.

Phages are found in a wide variety of places where bacteria exist including body fluids. The aim of the present study was to isolate phages from the urine samples of patients with urinary tract infection. The 10 urine samples were cultured to isolate bacteria and also used as phage sources against the isolated bacteria. From 10 urine samples with positive cultures, 3 phages were isolated (33%) and two of them were further studied. The Klebsiella phage GADU21 and Escherichia phage GADU22 phages infected Klebsiella pneumonia and Escherichia coli, respectively. Among the tested 14 species for host range analysis, the Klebsiella phage GADU21 was able to infect two species which are Klebsiella pneumonia and Proteus mirabilis, and Escherichia phage GADU22 was able to infect four species which are Shigella flexneri, Shigella sonnei and Escherichia coli. Among different isolates of the indicator bacteria for each phage, GADU21 infected half of the tested 20 Klebsiella pneumonia isolates while GADU22 infected 85% of the tested 20 E. coli isolates. The genome sizes and GC ratios were 75,968 bp and 44.4%, and 168,023 bp and 35.3% for GADU21 and GADU22, respectively. GADU21 and GADU22 were both lytic and had no antibiotic resistance and virulence genes. GADU21 was homologue with Klebsiella phage vB_KpP_FBKp27 but only 88% of the genome was covered by this phage. The non-covered parts of the GADU21 genome included genes for tail-fiber-proteins and HNH-endonuclease. GADU22 had 94.8% homology with Escherichia phage vB_Eco_OMNI12 and had genes for immunity proteins. Phylogenetic analysis showed GADU21 and GADU22 were members of Schitoviridae family and Efbeekayvirus genus and Straboviridae family and Tevenvirinae genus, respectively. VIRIDIC analysis classified these phages in new species clusters. Our study demonstrated the possibility to use infected body fluids as phage sources to isolate novel phages. GADU21 is the first reported Klebsiella phage isolated from human body fluid. The absence of virulence and antibiotic resistance genes in their genomes makes the phages a potential therapeutic tool against infections.

Clinical evaluation of metagenomic next-generation sequencing in unbiased pathogen diagnosis of urinary tract infection.

BACKGROUND: Early availability of pathogen identification in urinary tract infections (UTIs) has critical importance in disease management. Metagenomic next-generation sequencing (mNGS) has the potential to transform how acute and serious infections are diagnosed by offering unbiased and culture-free pathogen detection. However, clinical experience with application of the mNGS test is relatively limited. METHODS: We therefore established a MinION-based mNGS pathogens diagnostic platform and evaluated its potential for clinical implementation in UTIs with clinical samples. 213 urine samples from patients with suspected UTIs were included and subjected to mNGS testing using the MinION platform. mNGS results were compared to the gold standard of clinical culture and composite standard of combining clinical testing, confirmatory qPCR testing, and clinical adjudication by doctors. RESULTS: The mNGS exhibited a sensitivity of 81.4% and a specificity of 92.3%, along with a positive predictive value of 96.6%, a negative predictive value of 64.9%, and an overall accuracy of 84.4%, all of which were determined based on the gold standard of routine culture results. When assessed against the composite standard, the sensitivity and specificity both increased to 89.9% and 100%, respectively, while the accuracy rose to 92.4%. Notably, the positive predictive value and negative predictive value also saw improvements, reaching 100% and 76.8%, respectively. Moreover, this diagnostic platform successfully identified dsDNA viruses. Among the 65 culture-negative samples, the viral detection rate reached 33.8% (22/65) and was subsequently validated through qPCR. Furthermore, the automatic bioinformatics pipeline we developed enabled one-click analysis from data to results, leading to a significant reduction in diagnosis time. CONCLUSION: These results demonstrate that the pathogen detection performance of mNGS is sufficient for diagnostic testing in clinical settings. As the method is generally unbiased, it can improve diagnostic testing of UTIs and other microbial infections.

Primary Hyperoxaluria Type 3 Can Also Result in Kidney Failure: A Case Report.

Primary hyperoxaluria (PH) is a group of genetic disorders that result in an increased hepatic production of oxalate. PH type 3 (PH3) is the most recently identified subtype and results from mutations in the mitochondrial 4-hydroxy-2-oxoglutarate aldolase gene (HOGA1). To date, there have been 2 cases of kidney failure reported in PH3 patients. We present a case of a young man with a history of recurrent urinary tract infections and voiding dysfunction who developed kidney failure at 33 years of age. He developed a bladder stone and bilateral staghorn calculi at 12 years of age. Initial metabolic evaluation revealed hyperoxaluria with very low urinary citrate excretion on multiple measurements for which he was placed on oral citrate supplements. Further investigation of the hyperoxaluria was not completed as the patient was lost to follow-up observation until he presented at 29 years of age with chronic kidney disease stage 4 (estimated glomerular filtration rate 24mL/min/1.73m2). Hemodialysis 3 times a week was started at 33 years of age, and subsequent genetic testing revealed a homozygous HOGA1 mutation (C.973G>A p.Gly325Ser) diagnostic of PH3. The patient is currently being evaluated for all treatment options including possible liver/kidney transplantation. All cases of a childhood history of recurrent urinary stone disease with marked hyperoxaluria should prompt genetic testing for the 3 known PH types. Hyperhydration and crystallization inhibitors (citrate) are standard of care, but the role of RNA interference agents for all 3 forms of PH is also under active study.

Using an ATR-FTIR Technique to Detect Pathogens in Patients with Urinary Tract Infections: A Pilot Study.

Urinary tract infections (UTIs) are a leading hospital-acquired infection. Although timely detection of causative pathogens of UTIs is important, rapid and accurate measures assisting UTI diagnosis and bacterial determination are poorly developed. By reading infrared spectra of urine samples, Fourier-transform infrared spectroscopy (FTIR) may help detect urine compounds, but its role in UTI diagnosis remains uncertain. In this pilot study, we proposed a characterization method in attenuated total reflection (ATR)-FTIR spectra to evaluate urine samples and assessed the correlation between ATR-FTIR patterns, UTI diagnosis, and causative pathogens. We enrolled patients with a catheter-associated UTI in a subacute-care unit and non-UTI controls (total n = 18), and used urine culture to confirm the causative pathogens of the UTIs. In the ATR-FTIR analysis, the spectral variation between the UTI group and non-UTI, as well as that between various pathogens, was found in a range of 1800-900 cm-1, referring to the presence of specific constituents of the bacterial cell wall. The results indicated that the relative ratios between different area zones of vibration, as well as multivariate analysis, can be used as a clue to discriminate between UTI and non-UTI, as well as different causative pathogens of UTIs. This warrants a further large-scale study to validate the findings of this pilot research.

Developments in Mannose-Based Treatments for Uropathogenic Escherichia coli-Induced Urinary Tract Infections.

During their lifetime almost half of women will experience a symptomatic urinary tract infection (UTI) with a further half experiencing a relapse within six months. Currently UTIs are treated with antibiotics, but increasing antibiotic resistance rates highlight the need for new treatments. Uropathogenic Escherichia coli (UPEC) is responsible for the majority of symptomatic UTI cases and thus has become a key pathological target. Adhesion of type one pilus subunit FimH at the surface of UPEC strains to mannose-saturated oligosaccharides located on the urothelium is critical to pathogenesis. Since the identification of FimH as a therapeutic target in the late 1980s, a substantial body of research has been generated focusing on the development of FimH-targeting mannose-based anti-adhesion therapies. In this review we will discuss the design of different classes of these mannose-based compounds and their utility and potential as UPEC therapeutics.

d-Mannose Treatment neither Affects Uropathogenic Escherichia coli Properties nor Induces Stable FimH Modifications.

Urinary tract infections (UTIs) are mainly caused by uropathogenic Escherichia coli (UPEC). Acute and recurrent UTIs are commonly treated with antibiotics, the efficacy of which is limited by the emergence of antibiotic resistant strains. The natural sugar d-mannose is considered as an alternative to antibiotics due to its ability to mask the bacterial adhesin FimH, thereby preventing its binding to urothelial cells. Despite its extensive use, the possibility that d-mannose exerts "antibiotic-like" activity by altering bacterial growth and metabolism or selecting FimH variants has not been investigated yet. To this aim, main bacterial features of the prototype UPEC strain CFT073 treated with d-mannose were analyzed by standard microbiological methods. FimH functionality was analyzed by yeast agglutination and human bladder cell adhesion assays. Our results indicate that high d-mannose concentrations have no effect on bacterial growth and do not interfere with the activity of different antibiotics. d-mannose ranked as the least preferred carbon source to support bacterial metabolism and growth, in comparison with d-glucose, d-fructose, and l-arabinose. Since small glucose amounts are physiologically detectable in urine, we can conclude that the presence of d-mannose is irrelevant for bacterial metabolism. Moreover, d-mannose removal after long-term exposure did not alter FimH's capacity to bind to mannosylated proteins. Overall, our data indicate that d-mannose is a good alternative in the prevention and treatment of UPEC-related UTIs.

Associations between antibiotic prescriptions and recurrent urinary tract infections in female college students.

Urinary tract infections (UTIs) are common among college-aged women and often recur. Some antibiotics recommended to treat UTIs trigger dysbiosis of intestinal and vaginal microbiomes - where uropathogens originate, though few studies have investigated associations between these therapies with recurrent infections. We retrospectively analysed the electronic medical records of 6651 college-aged women diagnosed with a UTI at a US university student health centre between 2006 and 2014. Women were followed for 6 months for incidence of a recurrent infection. In a secondary analysis, associations in women whose experienced UTI recurrence within 2 weeks were also considered for potential infection relapse. Logistic regression was used to assess associations between infection recurrence or relapse and antibiotics prescribed, in addition to baseline patient characteristics including age, race/ethnicity, region of origin, year of encounter, presence of symptomology, pyelonephritis, vaginal coinfection and birth control consultation. There were 1051 instances of infection recurrence among the 6620 patients, indicating a prevalence of 16%. In the analysis of patient characteristics, Asian women were statistically more likely to experience infection recurrence whereas African American were less likely. No significant associations were identified between the antibiotic administered at the initial infection and the risk of infection recurrence after multivariable adjustment. Treatment with trimethoprim-sulphamethoxazole and being born outside of the USA were significantly associated with increased odds of infection relapse in the multivariate analysis. The results of the analyses suggest that treatment with trimethoprim-sulphamethoxazole may lead to an increased risk of UTI relapse, warranting further study.

Warmer weather as a risk factor for hospitalisations due to urinary tract infections.

The incidence of urinary tract infections (UTIs) is seasonal, and this seasonality may be explained by changes in weather, specifically, temperature. Using data from the Nationwide Inpatient Sample, we identified the geographic location for 581 813 hospital admissions with the primary diagnosis of a UTI and 56 630 773 non-UTI hospitalisations in the United States. Next, we used data from the National Climatic Data Center to estimate the monthly average temperature for each location. Using a case-control design, we modelled the odds of a hospital admission having a primary diagnosis of UTI as a function of demographics, payer, location, patient severity, admission month, year and the average temperature for the admission month. We found, after controlling for patient factors and month of admission, the odds of a UTI diagnosis increased with higher temperatures in a dose-dependent manner. For example, relative to months with average temperatures of 5-7.5 °C, an admission in a month with an average temperature of 27.5-30 °C has 20% higher odds of a primary diagnosis of UTI. However, in months with extremely high average temperatures (above 30 °C), the odds of a UTI admissions decrease, perhaps due to changes in behaviour. Thus, at a population level, UTI-related hospitalisations are associated with warmer weather.

Seasonality of urinary tract infections in the United Kingdom in different age groups: longitudinal analysis of The Health Improvement Network (THIN).

Evidence regarding the seasonality of urinary tract infection (UTI) consultations in primary care is conflicting and methodologically poor. To our knowledge, this is the first study to determine whether this seasonality exists in the UK, identify the peak months and describe seasonality by age. The monthly number of UTI consultations (N = 992 803) and nitrofurantoin and trimethoprim prescriptions (N = 1 719 416) during 2008-2015 was extracted from The Health Improvement Network (THIN), a large nationally representative UK dataset of electronic patient records. Negative binomial regression models were fitted to these data to investigate seasonal fluctuations by age group (14-17, 18-24, 25-45, 46-69, 70-84, 85+) and by sex, accounting for a change in the rate of UTI over the study period. A September to November peak in UTI consultation incidence was observed for ages 14-69. This seasonality progressively faded in older age groups and no seasonality was found in individuals aged 85+, in whom UTIs were most common. UTIs were rare in males but followed a similar seasonal pattern than in females. We show strong evidence of an autumnal seasonality for UTIs in individuals under 70 years of age and a lack of seasonality in the very old. These findings should provide helpful information when interpreting surveillance reports and the results of interventions against UTI.

Autovaccine-Based Immunotherapy: A Promising Approach for Male Recurrent Urinary Tract Infections.

BACKGROUND: Recurrent Urinary Tract Infections (UTIs) in men range from 0.9 to 2.4/1000 individuals in younger men to 7.7/1000 in those over 85, significantly impacting their quality of life. Preventive strategies include autovaccines, but limited evidence exists for males. METHODS: A prospective monocentric, open-label observational study was conducted from August 2018 to August 2021, with follow-up until August 2023 including patients with recurrent UTIs treated with immunotherapy. We evaluated the incidence rate of UTIs per year, the incidence rate of episodes after two or three rounds of the autovaccine, and quality of life measured with the IPSS-QoL questionnaire. RESULTS: A total of 49 patients fulfilled inclusion criteria. The mean age was 72 years (±15), and the median 61. The evolution of UTIs number of episodes after the autovaccine rounds: -37.74% for the first round from 5.3 to 3.3; -33.33% for the second round from 3.3 to 2.2; -45.45% for the third round from 2.2 to 1.2. The mean IPSS score improved from 10.69 to 7.27 after the treatment (32%). The mean QoL subscore enhancement was from 4.22 to 1.92 (54%). With a mean follow-up of 3 years, only nine patients required retreatment. CONCLUSION: Autovaccine treatment significantly reduced the number of UTI episodes, with a cumulative effect observed after multiple rounds of treatment, demonstrating an enhancement in QoL and with sustained effectiveness and a low need for retreatment.

Clinical Outcomes in Patients Who Received a One-Time Aminoglycoside Dose for Extended-Spectrum Beta-Lactamase-Producing Enterobacterales or Pseudomonas aeruginosa Cystitis.

The Infectious Diseases Society of America (IDSA) recommends a single dose of an aminoglycoside for uncomplicated cystitis caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) and difficult-to-treat Pseudomonas aeruginosa. However, there is very little recent clinical evidence to support this recommendation. The objective of this study was to evaluate the safety and efficacy of a single-dose aminoglycoside for cystitis caused by ESBL-E or Pseudomonas aeruginosa. This was a multicenter, retrospective, cohort study. Patients who received ≥3 days of standard of care were compared to patients who received a one-time dose of an aminoglycoside with or without a short course of effective therapy before. The primary outcome was the rate of relapse defined as requiring escalation of antibiotics or starting new antibiotic therapy within 14 days after the completion of antibiotics. A total of 66 patients were included in this study, with 33 patients in each arm. There were more males and complicated cystitis patients in the standard-of-care group. There was no difference found in the rate of relapse. The length of stay was significantly shorter in the aminoglycoside group (4.5 ± 4.4 days vs. 14.1 ± 10.1 days, p < 0.0001). A one-time dose of an aminoglycoside did not increase the risk of relapse and was associated with a shorter length of stay when used to treat cystitis caused by ESBL-E or Pseudomonas aeruginosa.

Antimicrobial Activity of Spices Popularly Used in Mexico against Urinary Tract Infections.

Urinary tract infections (UTIs) are the most common infectious diseases worldwide. These infections are common in all people; however, they are more prevalent in women than in men. The main microorganism that causes 80-90% of UTIs is Escherichia coli. However, other bacteria such as Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus mirabilis, and Klebsiella pneumoniae cause UTIs, and antibiotics are required to treat them. However, UTI treatment can be complicated by antibiotic resistance and biofilm formation. Therefore, medicinal plants, such as spices generally added to foods, can be a therapeutic alternative due to the variety of phytochemicals such as polyphenols, saponins, alkaloids, and terpenes present in their extracts that exert antimicrobial activity. Essential oils extracted from spices have been used to demonstrate their antimicrobial efficacy against strains of pathogens isolated from UTI patients and their synergistic effect with antibiotics. This article summarizes relevant findings on the antimicrobial activity of cinnamon, clove, cumin, oregano, pepper, and rosemary, spices popularly used in Mexico against the uropathogens responsible for UTIs.

Determination of microbiological characteristics and risk factors associated with bacteriuria and symptomatic urinary tract infection in patients with retained ureteral stents: an observational study.

Background: The maintenance of ureteral stents is vital in patients with severe ureteral stricture or ureteral obstruction. This study aimed to identify microbiological characteristics and factors associated with bacteriuria and symptomatic urinary tract infection (UTI) in these patients. Methods: This study is an observational cross-sectional study. From August 2018 to January 2021, urine samples from 307 consecutive patients who required stent indwelling and had replaced ureteral stents more than once were collected before the replacement procedure and analyzed by microbiological testing. Patient demographics, laboratory test results, and data on dependent functional capacity and indwelling urethral catheter use were collected from all patients. Additionally, ureteral stenting duration and number of previous ureteral stent replacements were reviewed. The primary endpoint was the incidence rate of bacteriuria and extended-spectrum beta-lactamase (ESBL)-producing bacteria. The secondary endpoint was the factors predisposing patients with ureteral stents to bacteriuria, ESBL-producing bacteria, and the development of symptomatic UTIs. Results: Bacteriuria was observed in 187 patients (60.9%). Among the bacteria identified in urine, Escherichia coli was the most commonly isolated microorganism, followed by Enterococcus, Candida species, Staphylococcus species, Klebsiella, and Pseudomonas. Using multivariate analysis, bacteriuria was significantly associated with old age, female sex, presence of diabetes mellitus, impaired renal function, and longer duration of ureteral stenting. ESBL-producing bacteria were detected in 52 isolates (27.8%). The incidence of ESBL-producing bacteria in urine culture was associated with old age and longer ureteral stenting duration. Additionally, symptomatic UTIs developed in 22 patients (7.2%). Dependent functional capacity, impaired renal function, and longer ureteral stenting duration were significantly associated with symptomatic UTIs. Conclusions: Infections related to ureteral stents showed a specific microorganism profile and resistance pattern compared to community-acquired UTIs. Additionally, we identified the factors associated with bacteriuria and symptomatic UTI in patients with retained ureteral stents and deduced that these may be associated with better outcomes in patients with retained ureteral stents.

Urinary tract infections: a review of the current diagnostics landscape.

Urinary tract infections are the most common bacterial infections worldwide. Infections can range from mild, recurrent (rUTI) to complicated (cUTIs), and are predominantly caused by uropathogenic Escherichia coli (UPEC). Antibiotic therapy is important to tackle infection; however, with the continued emergence of antibiotic resistance there is an urgent need to monitor the use of effective antibiotics through better stewardship measures. Currently, clinical diagnosis of UTIs relies on empiric methods supported by laboratory testing including cellular analysis (of both human and bacterial cells), dipstick analysis and phenotypic culture. Therefore, development of novel, sensitive and specific diagnostics is an important means to rationalise antibiotic therapy in patients. This review discusses the current diagnostic landscape and highlights promising novel diagnostic technologies in development that could aid in treatment and management of antibiotic-resistant UTIs.

Fast identification and susceptibility determination of E. coli isolated directly from patients' urine using infrared-spectroscopy and machine learning.

For effective treatment, it is crucial to identify the infecting bacterium at the species level and to determine its antimicrobial susceptibility. This is especially true now, when numerous bacteria have developed multidrug resistance to most commonly used antibiotics. Currently used methods need âˆ¼ 48 h to identify a bacterium and determine its susceptibility to specific antibiotics. This study reports the potential of using infrared spectroscopy with machine learning algorithms to identify E. coli isolated directly from patients' urine while simultaneously determining its susceptibility to antibiotics within âˆ¼ 40 min after receiving the patient's urine sample. For this goal, 1,765 E. coli isolates purified directly from urine samples were collected from patients with urinary tract infections (UTIs). After collection, the samples were tested by infrared microscopy and analyzed by machine learning. We achieved success rates of âˆ¼ 96% in isolate level identification and âˆ¼ 84% in susceptibility determination.

Effect of Mannan Oligosaccharides Extracts in Uropathogenic Escherichia coli Adhesion in Human Bladder Cells.

Urinary tract infections (UTIs) are a common public health problem, mainly caused by uropathogenic Escherichia coli (UPEC). Patients with chronic UTIs are usually treated with long-acting prophylactic antibiotics, which promotes the development of antibiotic-resistant UPEC strains and may complicate their long-term management. D-mannose and extracts rich in D-mannose such as mannan oligosaccharides (MOS; D-mannose oligomers) are promising alternatives to antibiotic prophylaxis due to their ability to inhibit bacterial adhesion to urothelial cells and, therefore, infection. This highlights the therapeutic potential and commercial value of using them as health supplements. Studies on the effect of MOS in UTIs are, however, scarce. Aiming to evaluate the potential benefits of using MOS extracts in UTIs prophylaxis, their ability to inhibit the adhesion of UPEC to urothelial cells and its mechanism of action were assessed. Additionally, the expression levels of the pro-inflammatory marker interleukin 6 (IL-6) were also evaluated. After characterizing their cytotoxic profiles, the preliminary results indicated that MOS extracts have potential to be used for the handling of UTIs and demonstrated that the mechanism through which they inhibit bacterial adhesion is through the competitive inhibition of FimH adhesins through the action of mannose, validated by a bacterial growth impact assessment.

Delineating the Diagnostic Concordance Between Pediatric Lower Urinary Symptoms Scoring and Voiding Diary in Pediatric Lower Urinary Tract Dysfunction.

BACKGROUND: This retrospective research endeavored to conduct a comparative evaluation of the Pediatric Lower Urinary Tract Symptoms Scoring (PLUTSS) system and the Voiding Diary (VD). The correlation between these diagnostic tools, their prognostic value for treatment outcomes in pediatric Lower Urinary Tract Dysfunction (LUTD), and their relationship with patients' sociodemographic characteristics were also explored. METHODOLOGY: The study data for the cohort established between December 2005 and September 2006 were obtained from a specialized thesis, while the subsequent expansion from 2022 to 2023 involved a prospective approach, including an additional 73 patients, resulting in a total of 113 pediatric patients (79 females and 34 males). Comprehensive diagnostic evaluations, such as urinalysis, urine culture, renal function tests, urinary tract ultrasound, uroflowmetry-electromyography (EMG), and post-voiding residual urine measurement (PVR), were conducted. The patient's symptoms were assessed using the Pediatric Lower Urinary Tract Symptom Score (PLUTSS) and a two-day-three-night voiding diary. RESULTS: The correlation between the PLUTSS and VD was not absolute but substantial concerning daytime frequency and incontinence. Notably, PLUTSS emerged as the primary predictor of treatment outcomes. No significant association was discerned between sociodemographic characteristics, such as socioeconomic status, sibling count, toilet training, school performance, patient personality, and LUTD diagnosis or prognosis. CONCLUSION: The findings underscore the prognostic value of PLUTSS for treatment outcomes in pediatric LUTD. Although a significant correlation was observed between PLUTSS and VD, they are not interchangeable. As a result, concurrent utilization of both tools is endorsed for comprehensive diagnosis, follow-up, and treatment planning in pediatric LUTD.

Into the understanding the multicellular lifestyle of Proteus mirabilis on solid surfaces.

Indwelling urinary catheterization can lead to the development of catheter-associated urinary tract infections (CAUTIs), an important type of nosocomial infection, as well as other medical issues among institutionalized adults. Recently, Proteus mirabilis was highlighted as the important cause of CAUTIs. The pathogenicity of P. mirabilis is dependent on two multicellular types of surface colonization: the adherence and swarming motility. Adhesion, mostly mediated by fimbrial and nonfimbrial adhesins, is important for the initiation of biofilm formation. Moreover, the production of urease frequently results in biofilm crystallization, which leads to the blockage of catheters. The heterologous polymeric matrix of the biofilm offers protection against antibiotics and the host immune system. P. mirabilis displays remarkable motility abilities. After contact with solid surfaces, hyper-flagellated cells are able to rapidly migrate. The importance of swarming motility in CAUTIs development remains controversial; however, it was indicated that swarming cells were able to co-express other virulence factors. Furthermore, flagella are strong immunomodulating proteins. On the other hand, both biofilm formation and swarming motility implicates multiple inter- and intraspecies interactions, which might contribute to the pathogenicity.

Rapid Detection of Bacterial Pathogens and Antimicrobial Resistance Genes in Clinical Urine Samples With Urinary Tract Infection by Metagenomic Nanopore Sequencing.

Urinary tract infections (UTIs) are among the most common acquired bacterial infections in humans. The current gold standard method for identification of uropathogens in clinical laboratories is cultivation. However, culture-based assays have substantial drawbacks, including long turnaround time and limited culturability of many potential pathogens. Nanopore sequencing technology can overcome these limitations and detect pathogens while also providing reliable predictions of drug susceptibility in clinical samples. Here, we optimized a metagenomic nanopore sequencing (mNPS) test for pathogen detection and identification in urine samples of 76 patients with acute uncomplicated UTIs. We first used twenty of these samples to show that library preparation by the PCR Barcoding Kit (PBK) led to the highest agreement of positive results with gold standard clinical culture tests, and enabled antibiotic resistance detection in downstream analyses. We then compared the detection results of mNPS with those of culture-based diagnostics and found that mNPS sensitivity and specificity of detection were 86.7% [95% confidence interval (CI), 73.5-94.1%] and 96.8% (95% CI, 82.4-99.9%), respectively, indicating that the mNPS method is a valid approach for rapid and specific detection of UTI pathogens. The mNPS results also performed well at predicting antibiotic susceptibility phenotypes. These results demonstrate that our workflow can accurately diagnose UTI-causative pathogens and enable successful prediction of drug-resistant phenotypes within 6 h of sample receipt. Rapid mNPS testing is thus a promising clinical diagnostic tool for infectious diseases, based on clinical urine samples from UTI patients, and shows considerable potential for application in other clinical infections.