Clinical Urinary Tract Infection Research Articles

Multicenter molecular investigation of recurrent Escherichia coli bacteriuria in dogs

Escherichia coli is the most common cause of recurrent urinary tract infection (UTI) in dogs. UTI recurrence comprises of persistent, unresolved E. coli infection or reinfection with a different strain of E. coli. Differentiating between these processes is clinically important but is often impossible with routine diagnostics.We tested the hypothesis that most recurrent canine E. coli bacteriuria is due to recurrence of the same E. coli strain involved in the initial infection.Molecular typing was performed on 98 urinary E. coli isolated from dogs with recurrent bacteriuria from five veterinary diagnostic laboratories in the United States.Of the 42 dogs in this study with multiple E. coli bacteriuria observations, a single strain of E. coli caused recurrent bacteriuria in 26 (62 %) dogs, in some cases on multiple occasions for prolonged periods of time (up to eight months). A single E. coli strain was detected during both subclinical bacteriuria and clinically-apparent UTI in three dogs. Isolates with the P-fimbrial adhesin genes papA and papC were associated with recurrence by the same strain of E. coli.Multiple isolations of a single strain of E. coli associated with recurrent bacteriuria suggests that E. coli may be maintained within the urinary tract of some dogs for prolonged periods of time. In some patients, the same strain can cause both clinical UTI and subclinical bacteriuria. This indicates that in dogs, the urinary bladder may serve as a subclinical, long-term reservoir of E. coli that may cause clinical UTI in the future.

Oxybutynin ameliorates LPS-induced inflammatory response in human bladder epithelial cells.

Urinary tract infection (UTI) mainly results from bacterial infections in the urinary tract and markedly impacts the normal lives of millions of patients worldwide. The infection and damage to urethral epithelial cells is the first and key step of UTI development and is a critical target for treating clinical UTI. Oxybutynin, an agent for treating urinary incontinence, is recently claimed with protective effects on bladder ultrastructure. Our study will assess the impact of Oxybutynin on inflammation in lipopolysaccharide (LPS)-stimulated bladder epithelial cells. Bladder epithelial T24 cells were treated with 1 μg/mL LPS with or without 10 and 20 μM Oxybutynin for 24 h. Increased levels of oxidative stress (OS) biomarkers, such as reactive oxygen species, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, as well as upregulated inducible nitric oxide synthase and promoted release of nitric oxide, were observed in LPS-managed T24 cells, all of which were signally suppressed by Oxybutynin. Furthermore, severe inflammatory responses, including enhanced release of cytokines, upregulated matrix metallopeptidase-2 (MMP-2) and MMP-9, and raised monocyte chemoattractant protein-1 level, were found in LPS-challenged T24 cells, which were markedly reversed by Oxybutynin. Moreover, the activated toll-1ike receptor 4/nuclear factor-κB pathway observed in LPS-managed T24 cells was repressed by Oxybutynin. Collectively, Oxybutynin mitigated LPS-induced inflammatory response in human bladder epithelial cells.

SARS-CoV-2 infection correlates with male benign prostatic hyperplasia deterioration.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) affects extra-respiratory systems, with small-scale studies showing worsened male lower urinary tract symptoms (LUTS) after coronavirus disease 2019 (COVID-19). This study explores the correlation between SARS-CoV-2 infection and male benign prostatic hyperplasia (BPH) complications using large-scale real world data. All male patients attending the public healthcare system in Hong Kong receiving alpha-blocker monotherapy for LUTS from 2021 to 2022 were included in this study. Patients with and without positive polymerase chain reaction (PCR) test for SARS-CoV-2 are selected as the exposure group and control group, respectively. Baseline characteristics are retrieved, with propensity score matching performed to ensure balance of covariates between the two groups. BPH complications were then compared and subgroup analyses were performed. After propensity score matching, 17,986 patients were included for analysis, among which half had PCR-confirmed SARS-CoV-2 infection (n=8993). When compared to controls, the SARS-CoV-2 group demonstrated statistically significant higher incidence of retention of urine (4.55% vs. 0.86%, p<0.001), haematuria (1.36% vs. 0.41%, p<0.001), clinical urinary tract infection (UTI) (4.31% vs. 1.49%, p<0.001), culture-proven bacteriuria (9.02% vs. 1.97%, p<0.001) and addition of 5ARI (0.50% vs. 0.02%, p<0.001). Subgroup analysis demonstrated similar differences across different age groups. There are no statistically significance differences in incidence of retention, haematuria, or addition of 5ARI across different COVID-19 severities. SARS-CoV-2 infection is associated with increased incidence of urinary retention, haematuria, UTI and the addition of combination therapy in the short term, regardless of COVID-19 severity. This is the largest study demonstrating the detrimental urological effects of SARS-CoV-2 infection.

Analysis of Antimicrobial Susceptibility in Bacterial Pathogens Associated with Urinary Tract Infections from Beijing Teaching Hospital in China, 2009-2017.

Since a urinary tract infection (UTI) is easy to relapse and difficult to treat, the antibiotic resistance rate has increased year by year in recent years. This study was to analyze the characteristics of the common pathogenic bacteria and the changes of antibiotic resistance in urinary system infection, so as to guide the standard use of antibiotics in a clinical urinary tract infection and control nosocomial infection effectively. A total of 5,669 strains of a urinary tract infection in the hospital from January 2009 to December 2017 were retrospectively analyzed. Bacterial identification and the antibiotic sensitivity test (AST) were analyzed by using a VITEK-2 Compact system. Of the 5669 pathogens, 3,256 (57.44%) of the strains were Gram-negative bacteria (GNB), 1,474 (26%) were Gram-positive bacteria (GPB), and 939 (16.56%) were fungi. Resistant rates of ESBL-producing strains were all significantly different from non-ESBL-producing strains in Escherichia coli (p < 0.05). The resistance rate of ESBL-producing strains to β-lactam antibiotics was all higher than that of non-ESBL-producing strains in Klebsiella pneumoniae (p < 0.05). The detection rate of vancomycin-resistantEnterococcus faecium and Enterococcus faecalis was 37.3% and 3.1%, respectively, and the detection rate of linezolid-resistantEnterococcus faecium and Enterococcus faecalis was 0.68% and 0%, respectively. The drug resistance rate of candida sp. to fluconazole, itraconazole, and voriconazole was 1.7%, 8.5%, and 3.4%, respectively. No amphotericin B-resistant strains were detected in the research. Among the 5669 strains isolated from urinary tract infection patients, GNB were the main pathogens. Escherichia coli was the major pathogen. The resistance rate of ESBLs-producingEscherichia coli was higher than that of non-ESBLs-producingEscherichia coli in general; meanwhile, β-lactam/β-lactamase inhibitors and carbapenems maintained good antimicrobial activity against Escherichia coli. The resistance rate of non-ESBLs-producingKlebsiella pneumoniae strains was significantly higher than that of ESBLs-producingKlebsiella pneumoniae strains, and drug resistance was more prominent; most of the antibiotic resistance rates were over 50%. The antimicrobial resistance rate of Enterococcus faecium was significantly higher than that of Enterococcus faecalis. There were rare linezolid-resistant strains. The antimicrobial resistance rate of imidazole to fungi was controlled less than 10%.

A double-blinded randomized placebo-controlled non-inferiority trial protocol for postoperative infections associated with canine pyometra

BackgroundPyometra is a common infectious condition, especially in elderly bitches. In addition to an infected uterus, dogs may have concurrent urinary tract infection (UTI). The preferred treatment is surgical removal of the ovaries and uterus, whereupon the general prognosis is excellent. In addition, antimicrobial therapy is frequently prescribed for postoperative treatment. However, no research exists on the benefit of postoperative antimicrobial treatment in uncomplicated canine pyometra. Antimicrobial resistance has become a major challenge in treatment of bacterial infections. Diminishing overuse of antimicrobial agents is essential for controlling the development of antimicrobial resistance in both animals and humans.MethodsThis double-blinded, randomized, placebo-controlled two-arm clinical trial is designed to compare the incidence of postoperative infections associated with surgical treatment of uncomplicated pyometra followed by two different treatment protocols. For the study, 150 dogs presenting with an uncomplicated pyometra and that are to undergo surgical treatment will be recruited. Dogs with body weight < 3 or > 93 kg, complicated pyometra, primary disease increasing the risk of infection, or immunosuppressive medication will be excluded. All dogs will receive one dose of sulfadoxine-trimethoprim intravenously as an antimicrobial prophylaxis. Postoperatively, dogs will be randomized to receive either a five-day course of placebo or an active drug, sulfadiazine-trimethoprim orally. During the surgery microbiological samples will be taken from urine and uterine content. The follow-up includes a control visit in 12 days and an interview of the owner 30 days after surgery. If bacteriuria is detected at the time of surgery, a urinary sample will be cultured for bacterial growth at the control visit. The primary outcome is the incidence of a postoperative surgical site infection (SSI), and the secondary outcome is the occurrence of clinical UTI with bacteriuria. Intention-to-treat and per-protocol analyses will be performed to compare outcome incidences between the treatment groups.DiscussionResearch-based evidence is necessary to create treatment guidelines for judicious use of antimicrobials. The goals of this study are to provide evidence for reducing the use of antimicrobials and targeting the treatment to patients proven to benefit from it. Publishing the trial protocol will increase transparency and promote open science practices.

MC-PRPA-HLFIA Cascade Detection System for Point-of-Care Testing Pan-Drug-Resistant Genes in Urinary Tract Infection Samples.

Recently, urinary tract infection (UTI) triggered by bacteria carrying pan-drug-resistant genes, including carbapenem resistance gene blaNDM and blaKPC, colistin resistance gene mcr-1, and tet(X) for tigecycline resistance, have been reported, posing a serious challenge to the treatment of clinical UTI. Therefore, point-of-care (POC) detection of these genes in UTI samples without the need for pre-culturing is urgently needed. Based on PEG 200-enhanced recombinase polymerase amplification (RPA) and a refined Chelex-100 lysis method with HRP-catalyzed lateral flow immunoassay (LFIA), we developed an MCL-PRPA-HLFIA cascade assay system for detecting these genes in UTI samples. The refined Chelex-100 lysis method extracts target DNA from UTI samples in 20 min without high-speed centrifugation or pre-incubation of urine samples. Following optimization, the cascade detection system achieved an LOD of 102 CFU/mL with satisfactory specificity and could detect these genes in both simulated and actual UTI samples. It takes less than an hour to complete the process without the use of high-speed centrifuges or other specialized equipment, such as PCR amplifiers. The MCL-PRPA-HLFIA cascade assay system provides new ideas for the construction of rapid detection methods for pan-drug-resistant genes in clinical UTI samples and provides the necessary medication guidance for UTI treatment.

Resuscitation dynamics reveal persister partitioning after antibiotic treatment.

Bacteria can survive antibiotics by forming dormant, drug-tolerant persisters. Persisters can resuscitate from dormancy after treatment and prolong infections. Resuscitation is thought to occur stochastically, but its transient, single-cell nature makes it difficult to investigate. We tracked the resuscitation of individual persisters by microscopy after ampicillin treatment and, by characterizing their dynamics, discovered that Escherichia coli and Salmonella enterica persisters resuscitate exponentially rather than stochastically. We demonstrated that the key parameters controlling resuscitation map to the ampicillin concentration during treatment and efflux during resuscitation. Consistently, we observed many persister progeny have structural defects and transcriptional responses indicative of cellular damage, for both β-lactam and quinolone antibiotics. During resuscitation, damaged persisters partition unevenly, generating both healthy daughter cells and defective ones. This persister partitioning phenomenon was observed in S.enterica, Klebsiella pneumoniae, Pseudomonas aeruginosa, and an E.coli urinary tract infection (UTI) isolate. It was also observed in the standard persister assay and after in situ treatment of a clinical UTI sample. This study reveals novel properties of resuscitation and indicates that persister partitioning may be a survival strategy in bacteria that lack genetic resistance.

Vesicoureteral reflux increases the risk of urinary tract infection prior to corrective surgery in newborn males with anorectal malformation.

The ideal colostomy type indicated for patients with anorectal malformation (ARM) is disputed. The aim of this study was to analyze the clinical factors associated with urinary tract infection (UTI) prior to corrective surgery in male ARM without perineal fistula having undergone diverting enterostomy. A retrospective review of patients diagnosed with ARM and surgically managed at our center from January 2011 to December 2019 was performed. Logistic regression was used to analyze the association between clinical factors and UTI. Eighty boys with ARM without perineal fistula underwent diverting enterostomy and subsequent corrective surgery via laparoscopic-assisted anorectal pull-through. A sigmoid loop colostomy was most often performed (70 patients, 87.5%). Twenty-nine patients (36.3%) were diagnosed with vesicoureteral reflux (VUR), including 14 (48.3%) with febrile UTIs. Six patients had other concomitant genitourinary anomalies excluding VUR. Multivariate logistic regression analysis revealed the presence of VUR as the only independent factor associated with the occurrence of febrile UTI (OR 17.3, 95% CI 3.51-85.26, p < 0.001). The development of UTI in newborn males with ARM is associated with the presence of VUR, regardless of stoma type. Voiding cystourethrography should be considered in patients with ARM for early diagnosis of VUR and subsequent antibiotic prophylaxis.

Cranberries after pelvic floor surgery for urinary tract infection prophylaxis: A randomized controlled trial.

Urinary tract infection (UTI) is a common complication after pelvic floor surgery. Antibiotics as prophylaxis may reduce the prevalence of UTI's by 50%, but bacterial resistance may be a large disadvantage, necessitating the search for other possible prophylactic options. Recent research found a 50% reduction in the rate of UTI's with the use of cranberry capsules after elective gynecologic surgery, suggesting that cranberry capsules may serve as a good prophylaxis. The aim of this study was to assess whether perioperative cranberry prophylaxis reduces the risk of clinical overt UTI after elective pelvic floor surgery with indwelling catheter. We conducted a single-center randomized, double-blind, placebo-controlled trial. Women were given cranberry capsules twice daily or identical placebo for 6 weeks, starting the day before surgery. The main endpoint of the trial was the incidence of UTI within 6 weeks after surgery, defined as clinical diagnosis and treatment of UTI by the medical doctor. Analyses were performed with the intention to treat. Two hundred ten participants were included, 105 in each arm. There was no significant difference in the prevalence of UTI between the cranberry arm (n = 13, 12.4%) and the placebo arm (n = 21, 20.0%; P = .13), but the prevalence in both arms was lower than anticipated. This trial shows no beneficial effect of adequately dosed cranberry prophylaxis in women undergoing pelvic floor surgery, although such effect cannot be ruled out in settings with a higher prevalence of UTI's.

Potential Probiotics Bacillus subtilis KATMIRA1933 and Bacillus amyloliquefaciens B-1895 Co-Aggregate with Clinical Isolates of Proteus mirabilis and Prevent Biofilm Formation

A urinary tract infection (UTI) is a multi-factorial disease including cystitis, pyelonephritis, and pyelitis. After Escherichia coli, Proteus mirabilis is the most common UTI-associated opportunistic pathogen. Antibiotic resistance of bacteria and infection recurrence can be connected to biofilm formation by P. mirabilis. In this study, human and sheep isolates of P. mirabilis were investigated for antibiotic sensitivity using an antibiotic disk test. Co-aggregation of the tested potential probiotic bacilli, Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933, with the isolated pathogen was also evaluated. Then, the anti-biofilm activity of naturally derived metabolites, such as subtilin and subtilosin, in the bacilli-free supernatants was assessed against biofilms of P. mirabilis isolates. The isolated pathogens were sensitive to 30μg of amikacin and 5μg of ciprofloxacin but resistant to other tested antibiotics. After 24h, auto-aggregation of B. amyloliquefaciens B-1895 was at 89.5% and higher than auto-aggregation of B. subtilis KATMIRA1933 (59.5%). B. amyloliquefaciens B-1895 strongly co-aggregated with P. mirabilis isolates from human UTIs. Cell-free supernatants of B. amyloliquefaciens B-1895 and B. subtilis KATMIRA1933 showed higher antimicrobial activity against biofilms of P. mirabilis isolated from humans as compared with biofilms of sheep isolates. According to our knowledge, this is the first report evaluating the anti-biofilm activity of probiotic spore-forming bacilli against clinical and animal UTI isolates of P. mirabilis. Further studies are recommended to investigate the anti-biofilm activity and the mode of action for the antimicrobial substances produced by these bacilli, subtilosin and subtilin.

Multiple Drug Resistant Urinary Tract Infection in Kidney Transplant Recipients: A Retrospective Cohort Study.

Urinary tract infection (UTI) is the most common infectious disease in post-kidney transplantation patients. The objective of the study was to investigate the prevalence, impact and risk factors of multiple drug resistant (MDR) UTI in kidney transplant recipients. This retrospective cohort study recruited 72 kidney transplant recipients between March 2017 and February 2018. Urine cultures performed during the 1st year of posttransplantation with reference to clinical data were evaluated. Predesigned questionnaire was used to collect data regarding demographic, transplant related, and microbiological information. Multivariate analysis was performed to ascertain risk factors of MDR UTI. Out of 72 patients, 28 (38.9%) had culture guided clinical UTI. Overall, 59 UTI episodes were noted throughout the duration of this study. Eschericia coli were found to be the most frequent uropathogen of UTI among kidney transplant recipients (n = 32, 54.2%). MDR bacteria were responsible for 27.1% (n = 16) of the post-transplantation UTI episodes among patients, with E. coli (n = 9, 56.3%) being the predominant bacterial pathogen. Most of the MDR strains of E. coli (n = 7, 77.8%) were extended spectrum beta-lactamase positive. Female gender (P <0.001), prolonged Foley's catheterization (P = 0.002), coexisting diabetes mellitus (DM) (P <0.001) and induction of anti-thymocyte globulin (ATG) therapy (P <0.001) were independently associated with high risk of MDR UTI. The allograft rejection was found to be significantly higher in patients of posttransplantation UTI with MDR uropathogen (P = 0.009). In conclusion, E. coli were the most prominent uropathogen of UTI with and without MDR pathogen in the present study. Female gender, prolonged Foley's catheterization, coexisting DM, and induction of ATG therapy were the risk factors independently associated with MDR UTI in kidney transplant recipients. MDR organisms were significantly associated with allograft rejection.

2180. Novel Method for Determining Rapid E.coli Antibiotic Susceptibility (AST) Results for Urinary Tract Infections

BackgroundMeasuring changes in phase noise from bacteria on a quartz crystal resonator has been shown to effectively distinguish viable from non-viable E. coli. We report using this method to rapidly perform AST for E. coli isolated from a leftover clinical urinary tract infection (UTI) specimen.MethodsAn experimental system was designed to sense changes in bacterial mechanics through changes in phase noise generated by bacterial cells (Figure 1). The system includes a quartz-crystal resonator with thin-film gold electrodes on opposite surfaces housed within a module. The module provides electrical contact to the crystal’s electrodes, and incorporates channels through which fluids can be pumped (Figure 2). E. coli was isolated from a leftover positive urine culture specimen, cultured overnight and resuspended in phosphate-buffered saline (PBS). The suspension was run through the experimental system. E.coli cells were adhered to the surface of the quartz resonant crystal coated with a cationic polymer. After a growth phase, the cells were exposed to antibiotic (ampicillin). Phase noise was monitored throughout the test. The power spectral density of the noise was averaged each 5 minutes. E.coli was classified as ampicillin susceptible if the spectral power of the added phase noise was at least 50% lower compared with controls. Controls were in growth media only (Figure 3). Automated microscopy was utilized to monitor cell growth.ResultsThe method correctly classified the E.coli as ampicillin susceptible. Power spectral density increased in untreated cells and dropped or stayed steady in cells treated with Ampicillin. Corresponding loss of E. coli viability was confirmed microscopically. Results were compared with standard of care antibiotic susceptibility testing.ConclusionThe phase noise measurement method correctly identified ampicillin susceptible E.coli isolated from a leftover patient urine sample in three and one half hours. It shows promise for providing rapid AST results to treat UTIs. Disclosures All authors: No reported disclosures.

Fosfomycin tromethamine activity on biofilm and intracellular bacterial communities produced by uropathogenic Escherichia coli isolated from patients with urinary tract infection.

Fosfomycin tromethamine (FT), an old antibiotic revived as a new strategy to overcome antibiotic resistance, is an excellent option for the treatment of lower urinary tract infection (UTI). During UTI, Escherichia coli produces biofilms and could invade the bladder epithelial cells, developing intracellular bacterial communities (IBC). The present work aimed to evaluate the activity of FT on biofilms and IBC from clinical isolates of E. coli. A total of 38 E. coli clinical UTI isolates previously characterized as biofilm and IBC producers were studied. FT susceptibility was evaluated and its activity on 48 h biofilm was determined by microtiter plate-based biofilm assay comparing three different antibiotic concentrations. Two UPEC strains were selected to evaluate FT activity on IBC in vitro using T24 bladder cells. The survival percentage of intracellular bacteria after 24 h exposure to FT was calculated and compared to the percentage of intracellular bacteria without antibiotic. All the strains were susceptible to FT. FT produced a significant reduction of biofilms at the three concentrations tested, compared to the control. However, no statistically effect on IBC was observed after 24 h of fosfomycin exposure in cell culture. FT is a good option for bacterial biofilm reduction within UTI. However, it does not affect IBC.

Prescription of antibiotics for urinary tract infection in general practice in Denmark

Objective: The aim of this study was to describe and characterize the prescription of antibiotics for urinary tract infection (UTI) in general practice in Denmark and to evaluate compliance with current recommendations.Design: National registry-based studySetting: Danish general practicePatients: 267.539 patients who redeemed a prescription for antibiotics with the clinical indication UTI at community pharmacies between July 1st 2012 and June 31st 2013.Main outcome measures: Antibiotics prescribed for 1) acute lower UTI, 2) acute upper UTI and 3) recurrent UTI presented as amount of prescriptions, number of treatments per 1000 inhabitants per day (TID) and defined daily doses per 1000 inhabitants per day (DID).Results: A total of 507.532 prescriptions were issued to 267.539 patients during the one year study period, representing 2.35 DID. Acute lower UTI was the most common reason for prescription of antibiotics (89.5%) followed by recurrent UTI (8.4%). The majority of the prescriptions were issued to people above 60 year old (57.6%). Pivmecillinam was the most commonly prescribed antibiotic in acute lower (45.8%) and acute upper (63.3%) UTI. Trimethroprim was the most commonly prescribed antibiotic in recurrent UTI (45.9%). Prescription of quinolones increased with increasing patient-age (p = <.0001).Conclusion: Compliance with current Danish recommendations was moderately high. Pivmecillinam is the first line antibiotic for the management of acute lower and upper UTI, and trimethroprim is the first line option of recurrent UTI. A high proportion of the antibiotic prescriptions were issued in the elderly population including a relatively high prescription rate of quinolones.Key pointsUrinary tract infection (UTI) is a common cause for prescription of antibiotics in general practicePoor compliance in general practice with recommendations for first-line treatment of UTI may increase antibiotic resistanceDanish general practitioners are generally compliant with national and regional guidelines for antibiotic treatment of UTIThere is high use of antibiotics in the elderly population including a worrisome high use of broad-spectrum antibiotics, such as Quinolones.

A Rapid and Low-Cost Pathogen Detection Platform by Using a Molecular Agglutination Assay.

Rapid and low-cost pathogen diagnostic approaches are critical for clinical decision-making procedures. Cultivating bacteria often takes days to identify pathogens and provide antimicrobial susceptibilities. The delay in diagnosis may result in compromised treatment and inappropriate antibiotic use. Over the past decades, molecular-based techniques have significantly shortened pathogen identification turnaround time with high accuracy. However, these assays often use complex fluorescent labeling and nucleic acid amplification processes, which limit their use in resource-limited settings. In this work, we demonstrate a wash-free molecular agglutination assay with a straightforward mixing and incubation step that significantly simplifies procedures of molecular testing. By targeting the 16S rRNA gene of pathogens, we perform a rapid pathogen identification within 30 min on a dark-field imaging microfluidic cytometry platform. The dark-field images with low background noise can be obtained using a narrow beam scanning technique with off-the-shelf complementary metal oxide semiconductor (CMOS) imagers such as smartphone cameras. We utilize a machine learning algorithm to deconvolute topological features of agglutinated clusters and thus quantify the abundance of bacteria. Consequently, we unambiguously distinguish Escherichia coli positive from other E. coli negative among 50 clinical urinary tract infection samples with 96% sensitivity and 100% specificity. Furthermore, we also apply this quantitative detection approach to achieve rapid antimicrobial susceptibility testing within 3 h. This work exhibits easy-to-use protocols, high sensitivity, and short turnaround time for point-of-care testing uses.

Synergistic Effect and Antibacterial Activities of Extracts of Salvia and Rosemary Officinalis Against Escherichia coli Isolated from Clinical Urinary Tract Infection

Background: Escherichia coli (E. coli) lives naturally in the human gut; however, emerging increase in bacterial resistance to antibiotics in some strains leads to chronic infection. Thus, more studies have recently focused on the characterization of potential plant natural antimicrobial agents, with fewer side effects. In the present study, antibacterial effects of salvia (teucrium polium) and rosemary officinalis extract have been evaluated against clinical isolated E. coli from urinary samples. Methods: In parallel with using Trimethoprim, Ceftriaxone, Cefixime, Cefotaxime, Ciprofloxacin, Gentamicin, Ceftazidime, and Meropenem against E. coli, salvia and rosemary plant extracts have also been used separately and in association with the antibiotics to detect the sensitivities of the bacteria to the components. Results: Salvia and rosemary had synergistic effects on ceftazidime against E. coli. The components decreased sensitivities of E. coli to some of the antibiotics. Conclusions: Based on the results, salvia and rosemary are able to increase anti-E. coli effects of ceftazidime and can be considered as future supplementary components against the bacteria.

The Effect of Cranberry Juice Consumption on the Recurrence of Urinary Tract Infection: Relationship to Baseline Risk Factors

ABSTRACTObjective: The objective of this study was to assess relationships between clinical predictors of urinary tract infection (UTI) and effects of cranberry juice consumption on recurrence in a post hoc analysis of a 24-week, randomized, double-blind, placebo-controlled, multicenter clinical trial in women with a recent history of UTI.Methods: Participants consumed a cranberry (n = 185) or placebo (n = 188) beverage (240 mL) daily. Odds ratios (OR) from 20 candidate predictor variables were evaluated in univariate analyses to assess clinical UTI incidence relationships in the placebo group. A multivariate logistic regression model was developed. The effects of cranberry juice consumption were evaluated in subsets categorized by the likelihood of a UTI event based on the prediction model.Results: In the placebo group, the final multivariate regression model identified four variables associated with the odds for having ≥ 1 UTI: intercourse frequency ≥ 1 time during the prior 4 weeks (OR: 2.36; 95% confidence interval [CI]: 0.98, 5.71; p = 0.057), use of vasectomy or hormonal methods for contraception (OR: 2.58; 95% CI: 1.20, 5.58; p = 0.016), most recent UTI < 90 days prior to screening (OR: 2.28; 95% CI; 1.12, 4.67; p = 0.024), and living in France compared with the United States (OR: 0.17; 95% CI: 0.04, 0.79; p = 0.024). Three propensity categories were investigated (24-week probability < 10%, 10%–21%, and > 21%). Incidence rate ratios for the cranberry vs placebo groups were 0.76 (95% CI: 0.22, 2.60; p = 0.663) for those with < 10% probability, 0.73 (95% CI: 0.35, 1.53; p = 0.064) for those with 10% to 21% probability, and 0.58 (95% CI: 0.35, 0.97; p = 0.039) for those with > 21% probability.Conclusions: Results suggest that clinical predictors identify women with low and high risk of clinical UTI recurrence, which may be useful for design of clinical studies evaluating preventive therapies.

Reassessing the utility of routine urine culture with urodynamics: UTI incidence and risk factors

There is no consensus regarding use of periprocedural antibiotics or routine urine cultures during urodynamics study (UDS) in children. At our hospital, we historically have obtained urine cultures during UDS. However, even with positive cultures, few patients require treatment. Most are successfully managed with increased hydration and frequent bladder emptying. To evaluate clinical characteristics, antibiotic treatment, and outcomes in patients undergoing UDS to identify (1) risk factors for urinary tract infection (UTI) after UDS, and (2) patients who may benefit from routine urine culture. Retrospective review of 769 patients who underwent 1057 UDS between January 2013 and January 2015. Positive urine culture was defined as ≥104 colony forming units/ml. Afebrile UTI was defined as new symptoms within 7 days. Febrile UTI was new symptoms with fever (≥38.5 °C). Fisher's exact test was used for comparative analyses. Nearly all patients had a urine culture taken immediately prior to UDS (94%, 993/1057). Patients on clean intermittent catheterization (CIC) were more likely to be on pre-UDS antibiotics, 22.8% (106/464) vs. 17.9% of those not on CIC (106/593) (p = 0.04). Of patients who had a urine culture, it was positive in 40% (402/993) with more positive cultures in patients on CIC vs. not (72.0%, 316/439 vs. 15.5%, 86/554, p < 0.0001). Factors significantly associated with clinical/possible post-UDS UTI included clinical UTI within 30 days before UDS, immunosuppression, overnight Foley catheter use, febrile UTI as indication, and symptoms on day of procedure (Table). Fifteen patients (1.4%, 95% confidence interval 0.7-2.1%) developed a clinical/possible post-UDS UTI, of which 40% (6/15) were febrile, with one requiring hospitalization. Of patients with post-UDS UTIs, 33% (5/15) had negative cultures at the time of UDS. If urine cultures were obtained selectively based on our study findings, 78% of pre-UDS urine cultures could be eliminated, while "missing" clinically relevant cultures in only 0.4% (4/1057). Study limitations include the retrospective design. However, prospective data collection will now be possible by using standardized, templated UDS and post-UDS follow-up notes with extractable data elements that automatically populate a database. Post-UDS UTI is uncommon (1.4%), even in the setting of bacteriuria. This finding calls into question the utility of routine pre-UDS urine culture. Data from this study and a future prospective study will be used to refine a new working protocol, with the goal of targeting future urine cultures to a high-risk subset of patients.

Cranberry Beverage Consumption Reduces Antibiotic Use for Clinical Urinary Tract Infection in Women with a Recent History of Urinary Tract Infection

Urinary tract infection (UTI) is one of the most commonly diagnosed types of bacterial infection, and is often treated with antibiotic therapy. Preventive approaches are needed to minimize unnecessary use of antibiotic therapy, which can contribute to the development of antibiotic resistant pathogens. The effect of the consumption of a daily cranberry beverage (240 mL/d; n = 185) compared to a placebo beverage (n = 188) on episodes of clinical UTI was investigated in a 24‐week, randomized, double‐blind, placebo‐controlled, multicenter clinical trial in women with a history of a recent UTI (Am J Clin Nutr 2016;103:1434–42; NCT01776021). The aim of this post‐hoc analysis was to evaluate the effect of consuming the cranberry beverage on the incidence of antibiotic use for treatment of three categories of clinical UTI: investigator‐diagnosed, probable UTI (subject was not examined by the investigator but a non‐study healthcare provider prescribed an antibiotic), and possible UTI (self‐administered antibiotic therapy). Investigator‐diagnosed episodes of clinical UTI were significantly reduced in the cranberry beverage group, relative to placebo (39 vs. 66; incidence rate ratio [IRR]: 0.63; 95% confidence interval [CI]: 0.42, 0.93; P = 0.021). There was a trend for reduced investigator‐diagnosed plus probable episodes of UTI in the cranberry group (47 vs. 71; IRR: 0.70; 95% CI: 0.48, 1.01; P = 0.056). Investigator‐diagnosed plus probable and possible episodes of UTI were significantly reduced in the cranberry group (47 vs. 73; IRR: 0.68; 95% CI: 0.47, 0.98; P = 0.038). The results of this post‐hoc analysis indicate that daily consumption of a cranberry beverage reduced the incidence of antibiotic treated clinical UTI in women with a recent history of UTI.Support or Funding InformationFunded by Ocean Spray Cranberries, Lakeville‐Middleboro, MA

Copper Is a Host Effector Mobilized to Urine during Urinary Tract Infection To Impair Bacterial Colonization.

Urinary tract infection (UTI) is a major global infectious disease affecting millions of people annually. Human urinary copper (Cu) content is elevated during UTI caused by uropathogenic Escherichia coli (UPEC). UPEC upregulates the expression of Cu efflux genes during clinical UTI in patients as an adaptive response to host-derived Cu. Whether Cu is mobilized to urine as a host response to UTI and its role in protection against UTI remain unresolved. To address these questions, we tested the hypothesis that Cu is a host effector mobilized to urine during UTI to limit bacterial growth. Our results reveal that Cu is mobilized to urine during UTI caused by the major uropathogens Proteus mirabilis and Klebsiella pneumoniae, in addition to UPEC, in humans. Ceruloplasmin, a Cu-containing ferroxidase, is found at higher levels in UTI urine than in healthy control urine and serves as the molecular source of urinary Cu during UTI. Our results demonstrate that ceruloplasmin decreases the bioavailability of iron in urine by a transferrin-dependent mechanism. Experimental UTI with UPEC in nonhuman primates recapitulates the increased urinary Cu content observed during clinical UTI. Furthermore, Cu-deficient mice are highly colonized by UPEC, indicating that Cu is involved in the limiting of bacterial growth within the urinary tract. Collectively, our results indicate that Cu is a host effector that is involved in protection against pathogen colonization of the urinary tract. Because urinary Cu levels are amenable to modulation, augmentation of the Cu-based host defense against UTI represents a novel approach to limiting bacterial colonization during UTI.