Recurrent Urinary Tract Infections In Women Research Articles

MV140 sublingual vaccine reduces recurrent urinary tract infection in women Results from the first North American clinical experience study.

This is the first North American clinical evidence for MV140, a novel bacterial sublingual vaccine, developed for prevention of recurrent urinary tract infection (UTI) in women. Female subjects with ≥3 documented UTIs/year underwent three-month vaccination treatment, nine-month efficacy period, and optional three-month followup (total 15 months). Primary outcome was no clinically diagnosed UTI following vaccination (UTI-free rate). Secondary outcomes included absolute, mean, and median overall reduction in UTI compared to pre-vaccination, quality of life, global response assessment, patient satisfaction, microbiology, and safety. Sixty-seven subjects (mean age 56 years, range 18-80) were enrolled; 64 completed the vaccination period and at least one post-vaccination assessment. Prior to vaccination, subjects reported a mean 6.8 UTIs/year. The UTI-free rate for the nine-month efficacy period was 40.6%. Compared to the infection rate in the year prior to vaccination, the reduction was 75.3% for the nine-month efficacy period post-vaccination. At 12-month followup, 80.3% reported that they were moderately/markedly improved; 58.1% were mostly satisfied, pleased, or delighted, while mean quality of life score improved by 1.5 points. Fourteen of the adverse events in nine subjects were potentially related to the vaccine - all mild and resolved by three months. None of the 13 serious adverse events were related to vaccine. This first-in-North-America, prospective case series with the sublingual vaccine, MV140, adds further clinical evidence to its safety and effectiveness in reducing recurrent UTIs in women.

Preventive effect of methenamine in women with recurrent urinary tract infections – a case–control study

Background Urinary tract infection (UTI) is the most common bacterial infection in women. In Norwegian general practice, methenamine has been prescribed for many years as long-term prevention and accounted for 20% of the total antibiotic prescribing in 2015, as measured in defined daily dosages (DDDs). The efficacy of methenamine is unknown. If shown to be effective, this drug may become an important preventive against UTI. Objective To examine whether methenamine is preventive against recurrent UTI in women. Design Data for all antibiotics used for UTIs dispensed from all pharmacies from 2005 to 2015 were collected from the Norwegian prescription database (NorPD). Subjects Women aged ≥ 40 years with recurrent UTI, defined as ≥3 courses of UTI antibiotic/year, were included. Main outcome measures Patients using methenamine (cases) and those not using methenamine (controls) were compared. The numbers of UTI prescriptions during the 2 years before and after inclusion were analysed. Results: The yearly prevalence for recurrent UTI was 2.4% in women ≥ 40 years. The change in antibiotic use from 2 years before to 2 years after inclusion in the study differed significantly between groups: 44.6 and 34.9% reductions in the number of antibiotic prescriptions for UTI in the methenamine and control groups, respectively. The decrease in UTI antibiotic prescriptions (58.9%) was greater in patients with a higher consumption of antibiotics before starting methenamine. Conclusions Methenamine seems to be effective against recurrent UTI over the time span studied. The effect seems to be greater in patients with the highest number of recurrent UTIs. Key points Methenamine has been used for many years for prevention of recurrent UTI, but no studies have demonstrated a significant preventive effect of long time use. This study shows that methenamine seems to be effective for prevention in patients having recurrent UTI over 2 years or more. The effect seems to be larger in patients with a high number of UTIs over 2 years.

Clinicopathological Analysis of Chronic Urothelial Inflammation Associated with UTI in Women

Introduction: Urinary tract infection (UTI) is a typical grumbling experienced in outpatient setting, regardless of whether essential care or expert facility. Objectives of the study: The basic aim of the study is to analyses the clinicopathological analysis of chronic urothelial inflammation associated with UTI in women. Material and methods: This cross sectional study was conducted in Foundation University Medical College Islamabad During March 2021 till November 2021. The data was collected through non-probability consecutive sampling technique. Results: The data was gathered from 100 patients. The examination of data shows the distinctions in urodynamic factors between the control subjects and the ESRD/CKD patients. In general, the ESRD/CKD patients had fundamentally lower FS, US, and CBC than did the controls. Patients with ESRD/CKD with DU had altogether lower FS, CBC in ESRD/DU patients with BO (table 01). Conclusion: It is concluded from our study that chronic inflammation, urothelial cell apoptosis and impairment of barrier function of urothelial cells could be the underlying pathophysiology of recurrent UTI in women. Keywords: UTI, Women, Pathology, Urothelial

Sublingual MV140 for Prevention of Recurrent Urinary Tract Infections

BackgroundRecurrent urinary tract infections (UTIs), which consist of three or more episodes in 1 year or two or more infections in 6 months, affect 5% to 10% of women. MV140, a sublingual preparation of whole-cell inactivated bacteria, has shown clinical benefit in observational studies. This trial examined treatment with MV140 to prevent recurrent UTI.MethodsIn this multicenter, randomized, double-blind, placebo-controlled, parallel-group 1-year trial, 240 women 18 to 75 years of age from Spain and the United Kingdom with recurrent UTI were allocated to receive MV140 for 3 or 6 months or placebo for 6 months in a 1:1:1 ratio. The primary end point was the number of UTIs in the 9-month study period after 3 months of intervention. Key secondary end points were the percentage of women who were UTI free over the above period, time to UTI onset, and health-related quality of life.ResultsThe median (interquartile range) of UTI episodes was 3.0 (0.5 to 6.0) for placebo compared with 0.0 (0.0 to 1.0) in both groups receiving MV140 (P<0.001). Among women treated with placebo, 25% (95% confidence interval [CI], 15% to 35%) were free of UTIs compared with 56% (95% CI, 44% to 67%) and 58% (95% CI, 44% to 67%) of women who received 3 and 6 months of MV140 treatment, respectively. A total of 205 AEs in 101 participants were registered (81, 76, and 48 in the placebo, 3-month MV140, and 6-month MV140 groups, respectively).ConclusionsIn this controlled trial of modest size and duration, MV140 showed promising clinical efficacy in reducing recurrent UTI in women suffering from this condition. Adverse effects were not clinically limiting. (Funded by Inmunotek S.L. and Syner-Med [Pharmaceutical Products] Ltd.; ClinicalTrials.gov number, NCT02543827.)

Management of uncomplicated recurrent urinary tract infections.

To discuss optimal management of recurrent urinary tract infections (UTIs) in women. About every second woman experiences at least one UTI in her lifetime, of those 30% experience another UTI, and 3% further recurrences. Especially young healthy women without underlying anatomical deficiencies suffer from recurrent UTIs (rUTI), which are associated with significant morbidity and reduction in quality of life. This is a narrative review, investigating publications dealing with recurrent UTI in women. Risk factors and options for management are discussed. The increased susceptibility of women to rUTI is based on the female anatomy in addition to behavioural, genetic, and urological factors. However, why some women are more likely than others to develop and maintain rUTI remains to be clarified. Invasive characteristics of certain uropathogenic Escherichia coli that are able to form extra- and intracellular biofilms and may therefore cause delayed release of bacteria into the bladder, may play a role in this setting. Treatment recommendations for an acute episode of rUTI do not differ from those for isolated episodes. Given the nature of rUTI, different prophylactic approaches also play an important role. Women with rUTI should first be counselled to use non-antibiotic strategies including behavioural changes, anti-adhesive treatments, antiseptics, and immunomodulation, before antibiotic prophylaxis is considered. In addition to the traditional treatment and prophylactic therapies, new experimental strategies are emerging and show promising effects, such as faecal microbiota transfer (FMT), a treatment option that transfers microorganisms and metabolites of a healthy donor's faecal matter to patients using oral capsules, enemas, or endoscopy. Initial findings suggest that FMT might be a promising treatment approach to interrupt the cycle of rUTI. Furthermore, bacteriophages, infecting and replicating in bacteria, have been clinically trialled for UTIs. Due to the limitation of available data, novel treatment options require further clinical research to objectify the potential in treating bacterial infections, particularly UTIs.

The evolution of recommendations for cranberry use in recurrent urinary tract infections: A systematic review

Abstract. Urinary tract infections (UTI) constitute a major complaint in medical offices worldwide, especially concerning women. Although the efficacy of cranberry in UTI prevention is still controversial it has long been recommended for use in clinical practice. Based on the recommendation evaluation, the present study aimed to conduct a systematic review to assess the efficacy of cranberry prophylaxis in recurrent UTIs in women. Main changes among reviewed publications revolved around the mechanism by which cranberry produce the results observed and once it was established that it relates to bacterial fimbriae-mediated adhesion, most authors now struggle to establish accurate measures to come up with a protocol for its use. Many studies compared cranberry effects to placebo and traditional antibiotic treatment and showed promising results about effectiveness, as well as economic drawbacks. Altogether, cranberries could help to delay ecological resistance to antibiotics as well as protect patients from infections. Further investigation, mainly regarding dosage, is needed to formulate protocols and safely introduce cranberries to clinical practice

Fosfomycin Prevents Intravenous Antibiotic Therapy in Women With Recurrent Urinary Tract Infections: A Retrospective Review.

The aim of this study was to evaluate the role of oral fosfomycin to prevent the use of intravenous (IV) antibiotic therapy in women with recurrent urinary tract infection (RUTI) complicated by antibiotic allergies and/or multidrug-resistant organisms. After institutional review board approval, a retrospective review of women prescribed fosfomycin for RUTI at our institution was performed. Excluded were patients who did not take fosfomycin. Data collected included demographics, baseline voiding function/urological anatomic abnormalities, need for IV antibiotic therapy for RUTI, RUTI-related surgery, antibiotic allergies, and urine culture results before and after taking fosfomycin. Success was defined as no subsequent IV antibiotic use for RUTI management after fosfomycin within the study follow-up. Secondary outcomes included time to next UTI after fosfomycin, time to next extended-spectrum beta-lactamase UTI, factors predicting failure, urine culture results after fosfomycin, and need for surgical intervention. Between 2013 and 2019, 105 women met study criteria. At a median follow-up (including phone interviews) of 1.7 years (interquartile range, 0.3-5.8) after fosfomycin, the success rate was 74%. Twenty-seven patients had documented sterile urine cultures immediately after fosfomycin. Prior history of hospitalization for UTI and infection with resistant organisms were predictive of failure. After fosfomycin, 25 women underwent bladder electrofulguration, and 3 required cystectomy. Fosfomycin reduced the rate of IV antibiotic therapy in the management of RUTI in women with multidrug-resistant organisms and/or antibiotic allergies. Fosfomycin was less effective in those with prior hospitalization for UTI or infection with resistant organisms.

Role of D-Mannose in the Prevention of Recurrent Uncomplicated Cystitis: State of the Art and Future Perspectives.

Background: Urinary tract infections (UTI) are highly frequent in women, with a significant impact on healthcare resources. Although antibiotics still represent the standard treatment to manage recurrent UTI (rUTI), D-mannose, an inert monosaccharide that is metabolized and excreted in urine and acts by inhibiting bacterial adhesion to the urothelium, represents a promising nonantibiotic prevention strategy. The aim of this narrative review is to critically analyze clinical studies reporting data concerning the efficacy and safety of D-mannose in the management of rUTIs. Methods: A non-systematic literature search, using the Pubmed, EMBASE, Scopus, Web of science, Cochrane Central Register of Controlled Trials, and Cochrane Central Database of Systematic Reviews databases, was performed for relevant articles published between January 2010 and January 2021. The following Medical Subjects Heading were used: “female/woman”, “urinary tract infection”, and “D-mannose”. Only clinical studies, systematic reviews, and meta-analyses reporting efficacy or safety data on D-mannose versus placebo or other competitors were selected for the present review. Evidence was limited to human data. The selected studies were organized in two categories according to the presence or not of a competitor to D-mannose. Results: After exclusion of non-pertinent studies/articles, 13 studies were analyzed. In detail, six were randomized controlled trials (RCTs), one a randomized cross-over trial, five prospective cohort studies, and one a retrospective analysis. Seven studies compared D-mannose to placebo or others drugs/dietary supplements. Six studies evaluated the efficacy of D-mannose comparing follow-up data with the baseline. D-mannose is well tolerated, with few reported adverse events (diarrhea was reported in about 8% of patients receiving 2 g of D-mannose for at least 6 months). Most of the studies also showed D-mannose can play a role in the prevention or rUTI or urodynamics-associated UTI and can overlap antibiotic treatments in some cases. The possibility to combine D-mannose with polyphenols or Lactobacillus seems another important option for UTI prophylaxis. However, the quality of the collected studies was very low, generating, consequently, a weak grade of recommendations as suggested by international guidelines. Data on D-mannose dose, frequency, and duration of treatment are still lacking. Conclusion: D-mannose alone or in combination with several dietary supplements or Lactobacillus has a potential role in the non antimicrobial prophylaxis or recurrent UTI in women. Despite its frequent prescription in real-life practice, we believe that further well-designed studies are urgently needed to definitively support the role of D-mannose in the management of recurrent UTIs in women.

Analysis of the Efficacy of a Sublingual Bacterial Vaccine in the Prophylaxis of Recurrent Urinary Tract Infection

Objectives: Recurrent urinary tract infections (R-UTIs) are very common amongst women, and alternatives to antibacterial prophylaxis are necessary. This study evaluates the effectiveness of a sublingual bacterial vaccine for the prophylaxis of R-UTIs. Methods: We conducted a quasi-experimental pretest-posttest study of 166 women diagnosed with R-UTIs. Both before and after the start of treatment with the vaccine, we analysed the total number of R-UTI episodes, the urine culture results, and the type and number of antibiotic packages consumed. Symptoms and urine cultures were evaluated 3, 6, 9, 12, 18, and 24 months after initiating treatment with the vaccine. Results: The mean time of follow-up after vaccination was 1.7 years. After vaccination, there was a 54.6% reduction in episodes of UTI, and a 56.2% reduction in positive urine cultures. At 3 months, 74.4% of the patients had no R-UTI, the rate falling to 68.1% at 6 months, 52.4% at 12 months, and 44.5% at 24 months. The cumulative probability of maintaining negative urine cultures was 76% at 3 months, 37% at 12 months, and 18% at 2 years. Conclusions: The use of a sublingual bacterial vaccine for the prophylaxis of R-UTIs in women is an effective treatment that contributes to a reduction in the number of UTI episodes.

Prevention and treatment of cystitis during menopause: efficacy of a nutraceutical containing D-mannose, inulin, cranberry, bearberry, Olea europaea, Orthosiphon and Lactobacillus acidophilus.

Aim of the studyTo evaluate the efficacy of a nutraceutical compound containing Uticlin® (D-mannose, cranberry, bearberry, Olea europaea), inulin, Orthosiphon and Lactobacillus acidophilus, in preventing recurrent urinary tract infections (UTIs) in menopausal women.Material and methodsThis was a prospective cohort study of menopausal women recruited with a history of recurrent UTIs in the previous twelve months and who intended to treat their bladder problem without the use of antibiotics and/or anti-inflammatories. Women were proposed the use of an oral nutraceutical compound. The drug was taken for ten days, every month. Women were assigned to two parallel cohorts: patients using (group 1) or not using (group 2) this nutraceutical compound. The primary objective of the study was to evaluate the number of women with less than two infective episodes in the 6-month follow-up and less than three episodes in the 12-month follow-up. The secondary endpoints were to evaluate the reduction of related symptoms at 12-month follow-up, according to the Visual Analog Scale (VAS).ResultsAt 6 months of therapy, the reduction in the number of patients with ≥ 2 UTIs was statistically significant (p < 0.05) compared to baseline only in group 1. At 12 months, the number of patients who were disease-free was significantly higher (p < 0.05) in group 1 compared to group 2. Moreover, the improvement of related symptoms was statistically significant (p < 0.05) in group 1, as shown by the reduction in the VAS scale value.ConclusionsIn menopausal women, the combination of D-mannose, inulin, cranberry, bearberry, Olea europaea, Orthosiphon and Lactobacillus acidophilus SGL 11 per os represents a useful therapy for recurrent UTIs in women wanting a natural approach.

Alternative to antibiotics for managing asymptomatic and non-symptomatic bacteriuria in older persons: a review.

Recurrent urinary tract infection (UTI) is one of the most common reasons for long-term antibiotic use in frail older people, and these individuals often have non-symptomatic bacteriuria. This article reviews the literature and recommendations for the treatment of UTIs particularly in the older population (>65 years). It considers the question: is there an alternative for antibiotics for asymptomatic and non-symptomatic bacteriuria in older adults? D-mannose powder has been recommended for the treatment of UTIs, as when applied locally, it reduces the adherence of Escherichia coli. In one study, D-mannose was reviewed for the prophylaxis of recurrent UTIs in women, and the findings indicated that it may be useful for UTI prevention instead of prophylactic antibiotics. There is a lack of information about the efficacy of cranberry products combined with D-mannose in this regard, and this is an area for further research.

Definition of Recurrent Urinary Tract Infections in Women: Which One to Adopt?

The aim of this study was to systematically review the various definitions of recurrent urinary tract infection (RUTI) recommended by experts and specialty societies cited in biomedical literature. A systematic review of RUTI in women was conducted using MEDLINE, EMBASE, and PubMed between 1966 and 2016 according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Statement. Twenty-five publications were selected for inclusion in this analysis. From review of included publications, 14 definitions of RUTI were obtained. Each source was searched for a textual definition of RUTI as well as presence or absence of specific key elements including urinary symptoms, colony forming unit count, bacterial species, number of UTIs per year, interval time between infections and a negative intervening culture. All data were reviewed by 2 separate investigators. The definition of RUTI was found highly variable in the literature. The tallying of key elements in included definitions suggests that a minimum RUTI definition should include urinary symptoms, urine culture colony forming unit/mL threshold, differentiation of bacterial persistence versus reinfection by bacterial species, and number of UTIs per year. This review of major RUTI definition recommendations by expert individuals and specialty societies underlines the lack of uniformity and the need for a more robust and generally agreeable RUTI definition for use in clinical and academic practice.

MP23-09 PRACTICE PATTERNS ACROSS SPECIALTIES IN THE TREATMENT OF WOMEN WITH RECURRENT UTIS IN AN ACADEMIC HEALTHCARE SYSTEM

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II1 Apr 2017MP23-09 PRACTICE PATTERNS ACROSS SPECIALTIES IN THE TREATMENT OF WOMEN WITH RECURRENT UTIS IN AN ACADEMIC HEALTHCARE SYSTEM Matthew Sterling, Eliza Lamin, Alexander Skokan, Alan Wein, and Ariana Smith Matthew SterlingMatthew Sterling More articles by this author , Eliza LaminEliza Lamin More articles by this author , Alexander SkokanAlexander Skokan More articles by this author , Alan WeinAlan Wein More articles by this author , and Ariana SmithAriana Smith More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.737AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recurrent urinary tract infections (UTIs) are a common problem managed by a variety of medical specialties. Several treatment strategies exist and no evidence-based pathway of care has been established. The objective of this investigation is to better understand the practice patterns for managing patients with recurrent UTIs in a tertiary care healthcare system. METHODS A 17-question electronic survey regarding the management of recurrent UTIs in women was distributed to 210 providers in the Internal Medicine (IM), Family Medicine (FM), Ob-Gyn (OBG), and Urology departments. Recurrent UTIs was defined as =3 in 1 year. RESULTS A total of 68 (32.3%) providers completed the survey. Sixty percent (39/65) of providers report treating patients with recurrent UTIs with an extended course of antibiotics. Additionally, 35% (23/65) of providers treat despite lack of symptoms and 37% (24/65) of providers utilize suppressive antibiotics. OBG and Urologists utilize suppressive antibiotics more than IM and FM at 50%. Of those providing suppressive antibiotics, 79% (19/24) chose nitrofurantoin. Providers refer to specialists after trying a median of 3 courses of antibiotics (IQR 3-4). Referral to Urologists was most common for concomitant stones (88%, 51/58) or hydronephrosis (78%, 45/58), whereas referral to Infectious Disease (ID) was most common for bacterial resistance (75%, 51/68) or multiple patient allergies (48.5%, 33/68). Overall, 91.2% (62/68) of providers felt a protocol for evaluating and managing recurrent UTIs would be useful. CONCLUSIONS Practice patterns for managing recurrent UTIs in female patients vary across and within specialties within the same healthcare system. There is limited data to suggest extended courses of antibiotics are effective for recurrent UTIs and may potentially contribute to increasing susceptibility to infection, yet this strategy is commonly employed in our healthcare system. Although referral patterns differ between Urologists and ID specialists, multiple antibiotics are employed prior to referral. The majority of providers believe a written protocol would improve patient care, reducing variability and improving quality. © 2017FiguresReferencesRelatedDetailsCited bySmith A, Brown J, Wyman J, Berry A, Newman D and Stapleton A (2018) Treatment and Prevention of Recurrent Lower Urinary Tract Infections in Women: A Rapid Review with Practice RecommendationsJournal of Urology, VOL. 200, NO. 6, (1174-1191), Online publication date: 1-Dec-2018. Volume 197Issue 4SApril 2017Page: e296 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Matthew Sterling More articles by this author Eliza Lamin More articles by this author Alexander Skokan More articles by this author Alan Wein More articles by this author Ariana Smith More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Probiotics for preventing urinary tract infections in adults and children.

Urinary tract infection (UTI) is a common bacterial infection that can lead to significant morbidity including stricture, abscess formation, fistula, bacteraemia, sepsis, pyelonephritis and kidney dysfunction. Mortality rates are reported to be as high as 1% in men and 3% in women due to development of pyelonephritis. Because probiotic therapy is readily available without a prescription, a review of their efficacy in the prevention of UTI may aid consumers in making informed decisions about potential prophylactic therapy. Institutions and caregivers also need evidence-based synopses of current evidence to make informed patient care decisions. Compared to placebo or no therapy, did probiotics (any formulation) provide a therapeutic advantage in terms of morbidity and mortality, when used to prevent UTI in susceptible patient populations?Compared to other prophylactic interventions, including drug and non-drug measures (e.g. continuous antibiotic prophylaxis, topical oestrogen, cranberry juice), did probiotics (any formulation) provide a therapeutic advantage in terms of morbidity and mortality when used to prevent UTIs in susceptible patient populations? We searched the Cochrane Kidney and Transplant Specialised Register to 21 September 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Randomised controlled trials (RCTs) of susceptible patients (e.g. past history of UTI) or healthy people in which any strain, formulation, dose or frequency of probiotic was compared to placebo or active comparators were included. All RCTs and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at comparing probiotics to no therapy, placebo, or other prophylactic interventions were included. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes. We included nine studies that involved 735 people in this review. Four studies compared probiotic with placebo, two compared probiotic with no treatment, two compared probiotics with antibiotics in patients with UTI, and one study compared probiotic with placebo in healthy women. All studies aimed to measure differences in rates of recurrent UTI.Our risk of bias assessment found that most studies had small sample sizes and reported insufficient methodological detail to enable robust assessment. Overall, there was a high risk of bias in the included studies which lead to inability to draw firm conclusions and suggesting that any reported treatment effects may be misleading or represent overestimates.We found no significant reduction in the risk of recurrent symptomatic bacterial UTI between patients treated with probiotics and placebo (6 studies, 352 participants: RR 0.82, 95% CI 0.60 to 1.12; I(2) = 23%) with wide confidence intervals, and statistical heterogeneity was low. No significant reduction in the risk of recurrent symptomatic bacterial UTI was found between probiotic and antibiotic treated patients (1 study, 223 participants: RR 1.12, 95% CI 0.95 to 1.33).The most commonly reported adverse effects were diarrhoea, nausea, vomiting, constipation and vaginal symptoms. None of the included studies reported numbers of participants with at least one asymptomatic bacterial UTI, all-cause mortality or those with at least one confirmed case of bacteraemia or fungaemia. Two studies reported study withdrawal due to adverse events and the number of participants who experienced at least one adverse event. One study reported withdrawal occurred in six probiotic participants (5.2%), 15 antibiotic participants (12.2%), while the second study noted one placebo group participant discontinued treatment due to an adverse event. No significant benefit was demonstrated for probiotics compared with placebo or no treatment, but a benefit cannot be ruled out as the data were few, and derived from small studies with poor methodological reporting.There was limited information on harm and mortality with probiotics and no evidence on the impact of probiotics on serious adverse events. Current evidence cannot rule out a reduction or increase in recurrent UTI in women with recurrent UTI who use prophylactic probiotics. There was insufficient evidence from one RCT to comment on the effect of probiotics versus antibiotics.

Interventions for preventing recurrent urinary tract infection during pregnancy.

Recurrent urinary tract infections (RUTI) are common in women who are pregnant and may cause serious adverse pregnancy outcomes for both mother and child including preterm birth and small-for-gestational-age babies. Interventions used to prevent RUTI in women who are pregnant can be pharmacological (antibiotics) or non-pharmacological (cranberry products, acupuncture, probiotics and behavioural modifications). So far little is known about the best way to prevent RUTI in pregnant women. To assess the effects of interventions for preventing RUTI in pregnant women.The primary maternal outcomes were RUTI before birth (variously defined) and preterm birth (before 37 weeks). The primary infant outcomes were small-for-gestational age and total mortality. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 May 2015) and reference lists of retrieved articles. Published, unpublished and ongoing randomised controlled trials (RCTs), quasi-RCTs, clustered-randomised trials and abstracts of any intervention (pharmacological and non-pharmacological) for preventing RUTI during pregnancy (compared with another intervention, placebo or with usual care). Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The review included one trial involving 200 women and was at moderate to high risk of bias.The trial compared a daily dose of nitrofurantoin and close surveillance (regular clinic visit, urine cultures and antibiotics when a positive culture was found) with close surveillance only. No significant differences were found for the primary outcomes: recurrent pyelonephritis (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.31 to 2.53; one study, 167 women), RUTI before birth (RR 0.30, 95% CI 0.06 to 1.38; one study, 167 women), and preterm birth (before 37 weeks) (RR 1.18, 95% CI 0.42 to 3.35; one study, 147 women). The overall quality of evidence for these outcomes as assessed using GRADE was very low. There were no significant differences between the two comparison groups for any of the following secondary outcomes, birthweight less than 2500 (g) (RR 2.03, 95% CI 0.53 to 7.80; one study, 147 infants), birthweight (mean difference (MD) -113.00, 95% CI -327.20 to 101.20; one study, 147 infants), five-minute Apgar score less than seven (RR 2.03, 95% CI 0.19 to 21.87; one study, 147 infants) and miscarriages (RR 3.11, 95% CI 0.33 to 29.29; one study, 167 women). The evidence for these secondary outcomes was also of very low quality. The incidence of asymptomatic bacteriuria (ASB) (at least 10(3) colonies per mL) (secondary outcome), only reported in women with a clinic attendance rate of more than 90% (RR 0.55, 95% CI 0.34 to 0.89; one study, 102 women), was significantly reduced in women who received nitrofurantoin and close surveillance. Data on total mortality and small-for-gestational-age babies were not reported. A daily dose of nitrofurantoin and close surveillance has not been shown to prevent RUTI compared with close surveillance alone. A significant reduction of ASB was found in women with a high clinic attendance rate and who received nitrofurantoin and close surveillance. There was limited reporting of both primary and secondary outcomes for both women and infants. No conclusions can be drawn regarding the optimal intervention to prevent RUTI in women who are pregnant. Randomised controlled trials comparing different pharmacological and non-pharmacological interventions are necessary to investigate potentially effective interventions to prevent RUTI in women who are pregnant.

Chinese herbal medicine for treating recurrent urinary tract infections in women.

Acute urinary tract infection (UTI) is a common bacterial infection that affects 40% to 50% of women. Between 20% and 30% of women who have had a UTI will experience a recurrence, and around 25% will develop ongoing recurrent episodes with implications for individual well-being and healthcare costs. Prophylactic antibiotics can prevent recurrent UTIs but there are growing concerns about microbial resistance, side effects from treatment and lack of long-term benefit. Consequently, alternative treatments are being investigated. Chinese herbal medicine (CHM) has a recorded history of treating UTI symptoms and more recent research suggests a potential role in the management of recurrent UTIs. This review aimed to evaluate CHM for recurrent UTI. This review assessed the benefits and harms of CHM for the treatment of recurrent UTIs in adult women, both as a stand-alone therapy and in conjunction with other pharmaceutical interventions. We searched the Cochrane Kidney and Transplant's Specialised Register to 7 May 2015 through contact with the Trials Search Co-ordinator, using search terms relevant to this review. We also searched AMED, CINAHL and the Chinese language electronic databases Chinese BioMedical Literature Database (CBM), China Network on Knowledge Infrastructure (CNKI), VIP and Wan Fang Databases to July 2014. We included randomised controlled trials (RCTs) comparing treatments using CHM with either an inactive placebo or conventional biomedical treatment. RCTs comparing different CHM strategies and treatments were eligible for inclusion.Quasi-randomised studies were excluded. Data extraction was carried out independently by two authors. Where more than one publication of one study existed, these were grouped and the publication with the most complete data was used in the analyses. Where relevant outcomes were only published in earlier versions these data were used. All meta-analyses were performed using relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). We included seven RCTs that involved a total of 542 women; of these, five recruited post-menopausal women (aged from 56 to 70 years) (422 women). We assessed all studies to be at high risk of bias. Meta-analyses comparing the overall effectiveness of treatments during acute phases of infection and rates of recurrence were conducted. Analysis of three studies involving 282 women that looked at CHM versus antibiotics suggested that CHM had a higher rate of effectiveness for acute UTI (RR 1.21, 95% CI 1.11 to 33) and reduced recurrent UTI rates (RR 0.28, 95% CI 0.09 to 0.82). Analysis of two studies involving 120 women that compared CHM plus antibiotics versus antibiotics alone found the combined intervention had a higher rate of effectiveness for acute UTI (RR 1.24, 95% CI 1.04 to 1.47) and resulted in lower rates of recurrent infection six months after the study (RR 0.53, 95% CI 0.35 to 0.80).One study comparing different CHM treatments found Er Xian Tang was more effective in treating acute infection in post-menopausal women than San Jin Pian (80 women: RR 1.28, 95% CI 1.03 to 1.57). Analysis showed that active CHM treatments specifically formulated for recurrent UTI were more effective in reducing infection incidence than generic CHM treatments that were more commonly used for acute UTI (RR 0.40, 95% CI 0.21 to 0.77).Only two studies undertook to report adverse events; neither reported the occurrence of any adverse events. Evidence from seven small studies suggested that CHM as an independent intervention or in conjunction with antibiotics may be beneficial for treating recurrent UTIs during the acute phase of infection and may reduce the recurrent UTI incidence for at least six months post-treatment. CHM treatments specifically formulated for recurrent UTI may be more effective than herbal treatments designed to treat acute UTI. However, the small number and poor quality of the included studies meant that it was not possible to formulate robust conclusions on the use of CHM for recurrent UTI in women either alone or as an adjunct to antibiotics.

Reply to Kaye and Sobel

To the Editor—In their letter [1], Kaye and Sobel express concern regarding the model described in our recent review [2] in which we suggest that recurrent urinary tract infections (UTIs) may in part be attributable to the ability of uropathogenic Escherichia coli (UPEC) to invade and persist within the bladder epithelium. This idea is based on results from numerous studies dating back to 1998 that used bladder cell cultures and mouse models of UTI [3]. In mice, persistent bacterial populations within the bladder are often intracellular, as assessed by gentamicin protection assays and microscopy, and unfazed by antibiotic treatments that effectively sterilize the urine. Ongoing studies in our lab and published work using mice indicate that these intracellular bacteria can reemerge sporadically and grow to high titers within the bladder lumen days to weeks after the cessation of antibiotic treatments (eg, [4–6]). The statement in our review that UPEC can persist intracellularly within the bladders of mice “without any overt clinical symptoms” was not the best choice of words and was perhaps too anthropomorphic [2]. We simply meant that mice could harbor intracellular UPEC reservoirs without displaying any obvious signs of inflammation and in the absence of any detectable bacteria within the urine. Epidemiological studies support the possibility that intracellular bacterial reservoirs within the urinary tract are responsible for many recurrent UTIs in women, but these data may also be explained by the persistence of UPEC reservoirs within local environments outside of the urinary tract (discussed in [7]). Ex vivo assays show that UPEC can invade human urothelial cells in tissue explants from volunteers, and the analysis of shed human urothelial cells collected from the urine of women with UTI symptoms indicates the presence of intracellular E. coli [8, 9]. Together, these sorts of observations suggest that intracellular UPEC reservoirs are likely more than a mouse-specific laboratory phenomenon. However, Kaye and Sobel are correct in noting that the ability of UPEC to persist long-term intracellularly within the human urinary tract has not been established. Determining if intracellular UPEC reservoirs contribute to recurrent UTIs within the human population is a daunting task, plagued by issues of tissue procurement and contamination, possible reinoculation of the bladder by UPEC from niches outside of the urinary tract, and limited means to accurately detect small numbers of bacteria within a relatively enormous tissue. Ultimately, defining the relevance of intracellular UPEC reservoirs to the etiology of recurrent UTIs may only come to light with the development of approaches that can eradicate the reservoirs. We of course agree with Kaye and Sobel that it is premature to alter treatment protocols for recurrent or chronic UTIs outside of controlled clinical investigations based solely on results from mice, but we also feel that it is important to consider alternate rational explanations for recalcitrant UTIs, whether or not they gibe with the traditional view that UPEC act as strictly extracellular pathogens.

The Effect of an Oral Probiotic Containing Lactobacillus, Bifidobacterium, and Bacillus Species on the Vaginal Microbiota of Spayed Female Dogs

Recurrent urinary tract infections (UTIs) are often difficult to treat. Vaginal colonization with lactic acid-producing bacteria (LAB) is associated with reduced frequency of recurrent UTIs in women. Oral probiotics might help increase the prevalence of vaginal LAB and decrease the frequency of recurrent UTIs in dogs. Administration of an oral probiotic supplement containing Lactobacillus, Bifidobacterium, and Bacillus species will increase the prevalence of LAB in the vagina of dogs. Thirty-five healthy, spayed female dogs without history of recurrent UTIs. Prospective, controlled study. Enrolled dogs received an oral probiotic supplement for 14 or 28 days. A vaginal tract culture was obtained from each dog before and after oral probiotic administration. Twenty-three dogs received the oral probiotic supplement daily for a period of 14 days and 12 dogs received the oral probiotic supplement daily for a period of 28 days. Lactic acid-producing bacteria were isolated from 7 of 35 dogs prior to probiotic administration. After the treatment course, 6 of 35 dogs had LAB isolated. Only one of these dogs had LAB (Enterococcus canintestini) isolated for the first time. Enterococcus canintestini was the most common LAB isolated from all dogs in this study, although it was not included in the probiotic supplement. Lactic acid-producing bacteria are not a common isolate from the vaginal vault of dogs. Administration of this oral probiotic supplement for a 2- or 4-week period did not increase the prevalence of vaginal LAB in dogs.

From physiology to pharmacy: developments in the pathogenesis and treatment of recurrent urinary tract infections.

Urinary tract infections (UTIs) are common, and over half of women report having had at least one in their lifetime. Nearly a third of these women experience recurrent UTI episodes, but the mechanisms of these recurrences are not fully elucidated. Frequent use of antimicrobials for treatment and prevention of UTIs and other infections has contributed to the evolution of multidrug-resistant microorganisms globally. This is a looming worldwide crisis that has created an urgent need for novel strategies for the treatment and prevention of UTIs. Furthering our understanding of the mechanisms of recurrent UTIs, from both host and bacterial perspectives, will be paramount in developing targeted management strategies. In this review, we discuss recent findings regarding recurrent UTIs in women, including progress in our understanding of the mechanisms of recurrence as well as emerging treatments.

Increased Urothelial Cell Apoptosis and Chronic Inflammation Are Associated with Recurrent Urinary Tract Infection in Women

ObjectiveThis study was designed to investigate whether increased urothelial cell apoptosis and chronic inflammation might contribute to recurrent urinary tract infection (UTI) in women.MethodsThe bladder biopsy specimens were collected from thirty women with recurrent UTI and ten controls. The bladder biopsies were performed at one to two months after UTI episode had been completely resolved and urine analysis and urine culture all showed negative. Immunofluorescence staining of the adhesive protein E-cadherin, mast cell and TUNEL were performed in all the bladder specimens. In addition, western blots were also performed to analyze the inflammatory proteins (phospho-p38, tryptase) and apoptotic protein (Bax) in the bladder mucosa specimens between patients with recurrent UTI and controls.ResultsImmunofluorescence staining showed significantly lower E-cadherin in the recurrent UTI bladder tissue compared with the controls (25.4±8.9 v 42.4±16.7, p<0.0001). The mast cell expression was significantly stronger in the recurrent UTI bladder tissue compared with the controls (2.5±1.8 v 1.3±1.2, p = 0.046). TUNEL staining revealed a significantly higher numbers of apoptotic cells in the recurrent UTI bladder tissue compared with the control bladder tissue (1.5±1.8 v 0.08±0.3, p<0.0001). Western blot analysis also showed that the expressions of tryptase and Bax increased in five recurrent UTI specimens compared with two normal control specimens.ConclusionChronic inflammation, urothelial cell apoptosis and impairment of barrier function of urothelial cells might contribute to recurrent UTI in women.