Uncomplicated Urinary Tract Infections Research Articles

Antibiotics efficacy in clinical and microbiological cure of uncomplicated urinary tract infection: a systematic review and network meta-analysis.

Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant bacteria. The aim of this network meta-analysis was to assess the efficacy of Fosfomycin compared to Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), and Ciprofloxacin in terms of clinical and microbiological cure alongside with other measurements. We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We included randomized control trials (RCTs) with uncomplicated UTI patients who received Fosfomycin, Nitrofurantoin, TMP-SMX, or Ciprofloxacin and reported the clinical or microbiological cure. We used Cochrane Risk of Bias Assessment Tool to assess the included studies' quality. R-software was used for all statistical analysis. We ranked all antibiotics using the netrank function which yielded P scores. Frequentist network meta-analysis was used to assess the efficacy of all outcomes. We included 13 RCTs with a total number of 3856 patients that showed Fosfomycin ranked the highest among the other antibiotics with respect to clinical cure (P-score = 0.99) and microbiological cure (P-score = 0.99) while Ciprofloxacin ranked the lowest (P-score = 0.11 and 0.02, respectively). Moreover, Ciprofloxacin yielded the highest relapse rate (P-score = 1), whereas TMP-SMX had the lowest relapse rate (P-score = 0.07). As for the adverse events, Ciprofloxacin demonstrated the highest adverse events as opposed to Fosfomycin (P-score = 0.98 and 0.05, respectively). The network meta-analysis demonstrated that Fosfomycin is the most effective antibiotic in treating uncomplicated UTIs with respect to clinical cure, microbiological cure, and adverse events profile.

Development of Predictive Models to Inform a Novel Risk Categorization Framework for Antibiotic Resistance in E. coli-Causing Uncomplicated Urinary Tract Infection.

In clinical practice, challenges in identifying patients with uncomplicated urinary tract infections (uUTIs) at risk of antibiotic non-susceptibility may lead to inappropriate prescribing and contribute to antibiotic resistance. We developed predictive models to quantify risk of non-susceptibility to four commonly prescribed antibiotic classes for uUTI, identify predictors of non-susceptibility to each class, and construct a corresponding risk categorization framework for non-susceptibility. Eligible females aged ≥12 years with E. coli-caused uUTI were identified from Optum's de-identified Electronic Health Record dataset (10/1/2015‒2/29/2020). Four predictive models were developed to predict non-susceptibility to each antibiotic class and a risk categorization framework was developed to classify patients' isolates as low, moderate, and high risk of non-susceptibility to each antibiotic class. Predictive models were developed among 87487 patients. Key predictors of having a non-susceptible isolate to ≥3 antibiotic classes included number of previous UTI episodes, prior β-lactam non-susceptibility, prior fluoroquinolone treatment, census bureau region, and race. The risk categorization framework classified 8.1%, 14.4%, 17.4%, and 6.3% of patients as having isolates at high risk of non-susceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, β-lactams, and fluoroquinolones, respectively. Across classes, the proportion of patients categorized as having high-risk isolates was 3-12 folds higher among patients with non-susceptible isolates versus susceptible isolates. Our predictive models highlight factors that increase risk of non-susceptibility to antibiotics for uUTIs, while the risk categorization framework contextualizes risk of non-susceptibility to these treatments. Our findings provide valuable insight to clinicians treating uUTIs and may help inform empiric prescribing in this population.

Immunoactive Prophylaxis Protocol of Uncomplicated Recurrent Urinary Tract Infections in a Cohort of 1104 Women Treated with Uromune® Vaccine

Background. A prospective, descriptive, and multicenter research that included 1104 women with three or more uncomplicated UTIs following immunoprophylaxis with Uromune® vaccine between 2011 and 2022 is presented. Methods. Objective: to analyze the efficacy of Uromune® and perform a follow-up protocol. Variables: age; bacteria; number of UTIs at baseline and at 3, 6, and 12 months of follow-up; distribution according to age and months of the year; therapy with polybacterial vaccine or autovaccine. Efficacy was defined as 0–2 UTIs during follow-up. Patients were divided into Group 1, with 3–4 UTIs at baseline, and Group 2, with 5 or more. Results. Average age was 72. Escherichia coli represented 64.3% of infections. Overall efficacy was 91.7%, 82.3%, and 57.6% at 3, 6, and 12 months. Efficacy in patients treated with vaccines was 95.8%, 88.4%, and 56.1%, and with autovaccines it was 85.7%, 73.6%, and 60.2%. Results were statistically significant in relation to vaccines (p < 0.05). Group 1 represented 65.2% and Group 2 represented 34.8%. Group 1 had an efficacy of 97.7%, 91.1%, and 64.7% and Group 2 had an efficacy of 80.2%, 64.3%, and 40%. Results were statistically significant in Group 1 (p < 0.05). Conclusions. Patients at baseline with less than five UTIs will have better result and would benefit from a prophylaxis protocol with Uromune®.

Lower Urinary Tract Infections: An Approach for Greek Community Health Practitioners

Urinary tract infections (UTIs) cause a significant infectious burden in the community and demand a coordinated approach from all first-line health professionals. Uncomplicated UTIs refer to infections in non-pregnant females without any underlying localized or generalized pathology, diagnosed through history by the presence of specific local symptoms and in the absence of systemic ones like fever. Uncomplicated UTIs are usually caused by Escherichia coli species; thus, empirical antibiotic treatment can be immediately initiated. A percentage of patients can experience a resolution of symptoms without therapy; however, this “wait and observe” approach is supported only by the relevant British guidelines. There are limited quality studies in the literature on adjuvant treatment options; these can include BNO 145, a phytotherapeutic medicine, and XHP, a medical technology product. Despite being licensed by the European Medicines Agency on the basis of traditional use, there is inadequate support in the medical literature for the use of cranberry extracts and Arctostaphylos uva-ursi extracts. The use of antibiotics is associated with higher response rates and urine culture sterilization as well as lower recurrence/relapse rates; on the other hand, side effect rates are also higher. In choosing the proper empirical antibiotic therapy, one has to take into account individual patient characteristics and community resistance patterns as well as the antimicrobial resistance pressure exerted by the wide use of a specific antibiotic. There is a need for a common framework through which all frontline health practitioners should operate when faced with a case of uncomplicated UTI. In Greece, there are three different guidelines for UTI treatment, developed by the Ministry of Health, the National Organization for Medicines, and the Hellenic Society for Infectious Diseases. The authors of the present study aim at synthesizing these guidelines as well as relevant guidelines from international scientific or other national regulatory organizations while taking into account local resistance patterns. The authors propose the first-line use of either fosfomycin, nitrofurantoin, or pivmecillinam. The use of trimethoprim/sulfamethoxazole is discouraged due to increased resistance of Greek community E. coli isolates. Fluoroquinolone use should be avoided due to high E. coli community resistance (exceeding 20% for Greece), along with their unfavorable benefit/side effect balance in uncomplicated UTIs, as well as the overall community resistance pressure exerted by their use. A 5-day regimen remains superior to a 3-day one; the latter may be suitable for certain, not yet adequately characterized, patients.

Reducing Antibiotic Duration for Uncomplicated UTI in the Pediatric Emergency Department.

Short-duration (3-5 days) antibiotic treatment of uncomplicated urinary tract infection (uUTI) in children >24 months of age is equivalent to longer-duration antibiotic treatment, with added benefits of antibiotic stewardship. At our pediatric emergency department (ED), 13% of 5- to 18-year-old patients discharged with uUTI received ≤5 days of antibiotics. We aimed to increase short-duration prescriptions in patients with uUTI from 13% to >50% over 12 months. This quality improvement project was conducted from January 2021 to August 2022. Complicated UTI was excluded. Interventions included education, practice feedback, and electronic health record changes. The outcome measure, the proportion of children treated with a short antibiotic duration, was studied by using p-charts. Antibiotic days saved were calculated. Revisits with UTI within 14 days of confirmed uUTI treated with short-duration antibiotics (balancing measure) were analyzed by using Fisher's exact test. In 1292 (n = 363 baseline, 929 post-intervention) eligible patients treated for uUTI, shorter antibiotic duration increased from 13% to 91%. We met our 50% aim within 2 months, with continued improvement leading to an additional centerline shift. Consequently, 2619 antibiotic days were saved. Two of 334 (0.6%) patients returned (P = NS) within 14 days of the index visit with a culture-positive uUTI. By using education, feedback, and electronic health record changes, we decreased antibiotic duration in children discharged from the ED for uUTI without a significant increase in return visits with UTI. These interventions can be expanded to wider age groups and other outpatient settings.

Cefazolin as a predictor of urinary cephalosporin activity in indicated Enterobacterales.

Traditionally, cephalothin susceptibility results were used to predict the susceptibility of additional cephalosporins; however, in 2013-2014, the Clinical and Laboratory Standards Institute (CLSI) revisited this practice and determined that cefazolin is a more accurate proxy than cephalothin for uncomplicated urinary tract infections (uUTIs). Therefore, a cefazolin surrogacy breakpoint was established to predict the susceptibility of seven oral cephalosporins for Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis in the context of uUTIs. Clinical microbiology laboratories face several operational challenges when implementing the cefazolin surrogacy breakpoint, which may lead to confusion for the best path forward. Here, we review the historical context and data behind the surrogacy breakpoints, review PK/PD profiles for oral cephalosporins, discuss challenges in deploying the breakpoint, and highlight the limited clinical outcome data in this space.

Multidrug resistance among uropathogenic clonal group A E. Coli isolates from Pakistani women with uncomplicated urinary tract infections

ObjectiveMulti-drug resistance (MDR) has notably increased in community acquired uropathogens causing urinary tract infections (UTIs), predominantly Escherichia coli. Uropathogenic E. coli causes 80% of uncomplicated community acquired UTIs, particularly in pre-menopausal women. Considering this high prevalence and the potential to spread antimicrobial resistant genes, the current study was conducted to investigate the presence of clinically important strains of E. coli in Pakistani women having uncomplicated cystitis and pyelonephritis. Women belonging to low-income groups were exclusively included in the study. Seventy-four isolates from urine samples were processed, phylotyped, and screened for the presence of two Single Nucleotide Polymorphisms (SNPs) particularly associated with a clinically important clonal group A of E. coli (CgA) followed by antibiotic susceptibility testing and genome sequence analysis.ResultsPhylogroup B2 was most prevalent in patients and 44% of isolates were positive for the presence of CgA specific SNPs in Fumarate hydratase and DNA gyrase subunit B genes. Antibiotic susceptibility testing showed widespread resistance to trimethoprim-sulfamethoxazole and extended-spectrum beta-lactamase production. The infection analysis revealed the phylogroup B2 to be more pathogenic as compared to the other groups. The genome sequence of E. coli strain U17 revealed genes encoding virulence, multidrug resistance, and host colonization mechanisms.ConclusionsOur research findings not only validate the significant occurrence of multidrug-resistant clonal group A E. coli (CgA) in premenopausal Pakistani women suffering from cystitis and pyelonephritis but also reveal the presence of genes associated withvirulence, and drug efflux pumps. The detection of highly pathogenic, antimicrobial-resistant phylogroup B2 and CgA E. coli strains is likely to help in understanding the epidemiology of the pathogen and may ultimately help to reduce the impact of these strains on human health. Furthermore, the findings of this study will particularly help to reduce the prevalence of uncomplicated UTIs and the cost associated with their treatment in women belonging to low-income groups.

Interactions between Gepotidacin and Escherichia coli Gyrase and Topoisomerase IV: Genetic and Biochemical Evidence for Well-Balanced Dual-Targeting.

Antimicrobial resistance is a global threat to human health. Therefore, efforts have been made to develop new antibacterial agents that address this critical medical issue. Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial in clinical development. Recently, phase III clinical trials for gepotidacin treatment of uncomplicated urinary tract infections caused by uropathogens, including Escherichia coli, were stopped for demonstrated efficacy. Because of the clinical promise of gepotidacin, it is important to understand how the compound interacts with its cellular targets, gyrase and topoisomerase IV, from E. coli. Consequently, we determined how gyrase and topoisomerase IV mutations in amino acid residues that are involved in gepotidacin interactions affect the susceptibility of E. coli cells to the compound and characterized the effects of gepotidacin on the activities of purified wild-type and mutant gyrase and topoisomerase IV. Gepotidacin displayed well-balanced dual-targeting of gyrase and topoisomerase IV in E. coli cells, which was reflected in a similar inhibition of the catalytic activities of these enzymes by the compound. Gepotidacin induced gyrase/topoisomerase IV-mediated single-stranded, but not double-stranded, DNA breaks. Mutations in GyrA and ParC amino acid residues that interact with gepotidacin altered the activity of the compound against the enzymes and, when present in both gyrase and topoisomerase IV, reduced the antibacterial activity of gepotidacin against this mutant strain. Our studies provide insights regarding the well-balanced dual-targeting of gyrase and topoisomerase IV by gepotidacin in E. coli.

Dipsticks and point-of-care Microscopy to reduce antibiotic use in women with an uncomplicated Urinary Tract Infection (MicUTI): protocol of a randomised controlled pilot trial in primary care

IntroductionUncomplicated urinary tract infections (uUTIs) in women are common infections encountered in primary care. Evidence suggests that rapid point-of-care tests (POCTs) to detect bacteria and erythrocytes in urine at presentation...

Likelihood of Antimicrobial Resistance in Urinary E. coli Isolates among US Female Patients with Recurrent vs Non-Recurrent Uncomplicated Urinary Tract Infection

ObjectivesTo assess the relative likelihood of antimicrobial resistance (AMR) and multi-drug resistance (MDR) among E. coli isolates from outpatients with recurrent versus non-recurrent uncomplicated urinary tract infection (uUTI). MethodsIn this retrospective observational US cohort study, female outpatients (≥12 years) with uUTI, positive E. coli culture, and treated with ≥1 oral antibiotic within ±5 days of diagnosis were grouped into recurrent and non-recurrent uUTI cohorts per their UTI history (past 12 months). AMR to specific drug classes was evaluated at index. Univariable and multivariable logistic regression models estimated the likelihood of not-susceptible E. coli isolates (AMR/MDR) among patients with recurrent uUTI versus non-recurrent uUTI. ResultsRecurrent (N=12,234) and non-recurrent (N=68,033) uUTI cohorts had similar distributions (race, ethnicity, region). Patients with recurrent uUTI had a higher prevalence of E. coli resistance to trimethoprim-sulfamethoxazole (21.8% vs 18.7%) and fluoroquinolones (14.2% vs 8.6%), and more isolates were extended-spectrum β-lactamase-producing (5.9% vs 4.1%) compared to non-recurrent uUTI patients. Patients with recurrent uUTI had a higher likelihood (odds ratio [95% confidence interval]) of any AMR (1.28 [1.22–1.34]), single drug-class resistance (1.18 [1.12–1.24]), and resistance to 2 (1.53 [1.41–1.67]) or ≥ 3 drug classes (1.70 [1.48–1.96]) (all P<0.001). ConclusionsThis study delineated the likelihood of AMR and MDR among E. coli isolates from patients with recurrent versus non-recurrent uUTI. While some treatment guidelines support empiric therapy in recurrent uUTI, the increased likelihood of resistance among these patients suggests that culture and susceptibility testing should be undertaken to inform recurrent uUTI treatment.

Exploring general practitioners' decision-making in the management of women with uncomplicated urinary tract infections: a qualitative study.

To be effective, interventions aiming at increasing the appropriateness of antibiotic use in primary care should consider the perspectives of prescribing physicians. To explore the decision-making of general practitioners (GPs) when managing uncomplicated urinary tract infections (uUTIs) in women. Semi-structured interviews with 22 GPs in Bavaria and Baden-Wurttemberg (southern Germany). Verbatim transcripts analysed through inductive qualitative content analysis. We generated three main themes: factors facilitating the decision-making, factors complicating the decision-making, and consultation modalities. According to participants, following evidence-based recommendations makes the prescription decision smoother. GPs' and patients' prior experiences and beliefs guides decisions towards certain antibiotics, even if those experiences and beliefs contradict evidence-based recommendations. Patient expectations and demands also conditions antibiotic prescribing, favouring it. Organisational constraints like time pressure, the day of the week (eg, before weekends) and a lower cost of antibiotics for patients than alternative treatments favour the decision to prescribe antibiotics. Diagnostic and prognostic uncertainty complicates decision-making, as does scepticism towards evidence-based recommendations. Discordance within the patient-doctor relationship contributed to this complexity. Regarding consultation modalities, a more in-depth consultation, and shared decision-making were seen as helpful in this process. We identified different factors as intervening against or for a straightforward management decision when dealing with women with uUTIs. They reveal the complexity behind the GPs' decision-making. Providing GPs with easy-to-apply guidance while removing economic constraints to allocate sufficient consultation time, and supporting shared decision-making may help GPs appropriately manage uUTIs in women.

Prevalence, regional distribution, and trends of antimicrobial resistance among female outpatients with urine Klebsiella spp. isolates: a multicenter evaluation in the United States between 2011 and 2019

BackgroundAntimicrobial resistance research in uncomplicated urinary tract infection typically focuses on the main causative pathogen, Escherichia coli; however, little is known about the antimicrobial resistance burden of Klebsiella species, which can also cause uncomplicated urinary tract infections. This retrospective cohort study assessed the prevalence and geographic distribution of antimicrobial resistance among Klebsiella species and antimicrobial resistance trends for K. pneumoniae in the United States (2011–2019).MethodsK. pneumoniae and K. oxytoca urine isolates (30-day, non-duplicate) among female outpatients (aged ≥ 12 years) with presumed uUTI at 304 centers in the United States were classified by resistance phenotype(s): not susceptible to nitrofurantoin, trimethoprim/sulfamethoxazole, or fluoroquinolone, extended-spectrum β-lactamase-positive/not susceptible; and multidrug-resistant based on ≥ 2 and ≥ 3 resistance phenotypes. Antimicrobial resistance prevalence by census division and age, as well as antimicrobial resistance trends over time for Klebsiella species, were assessed using generalized estimating equations.Results270,552 Klebsiella species isolates were evaluated (250,719 K. pneumoniae; 19,833 K. oxytoca). The most frequent resistance phenotypes in 2019 were nitrofurantoin not susceptible (Klebsiella species: 54.0%; K. pneumoniae: 57.3%; K. oxytoca: 15.1%) and trimethoprim/sulfamethoxazole not susceptible (Klebsiella species: 10.4%; K. pneumoniae: 10.6%; K. oxytoca: 8.6%). Extended-spectrum β-lactamase-positive/not susceptible prevalence was 5.4%, 5.3%, and 6.8%, respectively. K. pneumoniae resistance phenotype prevalence varied (p < 0.0001) geographically and by age, and increased over time (except for the nitrofurantoin not susceptible phenotype, which was stable and > 50% throughout).ConclusionsThere is a high antimicrobial resistance prevalence and increasing antimicrobial resistance trends among K. pneumoniae isolates from female outpatients in the United States with presumed uncomplicated urinary tract infection. Awareness of K. pneumoniae antimicrobial resistance helps to optimize empiric uncomplicated urinary tract infection treatment.

Cefdinir vs cephalexin for the treatment of urinary tract infections: A retrospective evaluation.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Cefdinir and cephalexin are cephalosporin antibiotics commonly used in the treatment of urinary tract infections (UTIs). Their efficacy depends on achieving sufficient time with concentrations exceeding the minimum inhibitory concentration (MIC). Despite being frequently prescribed for UTIs, cefdinir has markedly lower urine penetration compared to cephalexin. It is possible that differences in pharmacokinetics could result in dissimilar efficacy between these agents; however, comparative studies of cephalosporins in UTIs are lacking. This was a retrospective comparative study of patients discharged from emergency departments within a community health system with a diagnosis of acute cystitis who were prescribed cefdinir or cephalexin. Treatment failure rates at 7 and 14 days were compared between the 2 agents using a χ2 or Fisher's exact test, as appropriate. There were no differences in overall treatment failure between the cefdinir and cephalexin groups. Treatment failure at 7 days occurred in 11.6% (n = 14) of patients in the cefdinir group and 8.3% (n = 10) of patients in the cephalexin group (P = 0.389). Treatment failure at 14 days was higher for cefdinir at 20.7% (n = 25) than for cephalexin at 11.8% (n = 14), but this difference was not statistically significant (P = 0.053). There were no differences in the rate of treatment failure in subgroup analyses of uncomplicated or complicated UTIs. The results of this study suggest that cefdinir and cephalexin have comparable efficacy for the treatment of lower UTIs. While there was a numerically higher rate of treatment failure with cefdinir, there were no significant differences in treatment failure between the agents.

Comprehensive Review of Urinary Tract Infections in Renal Transplant Recipients: Clinical Insights and Management Strategies.

Urinary tract infections (UTIs) pose a significant challenge in the care of renal transplant recipients. This comprehensive review explores this population's multifaceted landscape of UTIs, emphasizing the importance of early diagnosis and tailored management strategies. Renal transplant recipients face an elevated risk of UTIs due to immunosuppression, altered urinary tract anatomy, and complex comorbidities. Complications of UTIs can lead to graft dysfunction and systemic illness, underscoring the need for effective management. The emergence of multidrug-resistant uropathogens adds complexity to treatment, highlighting the importance of targeted antibiotic therapy. Antibiotics are the most commonly prescribed drugs for UTIs, with nitrofurantoin, fosfomycin, amoxicillin, and amoxicillin-clavulanate potassium being some of the commonly used antibiotics. However, the emergence of multidrug-resistant uropathogens has led to the exploration of alternative treatments, such as bacteriophage therapy, as a potential alternative against multidrug-resistant uropathogenic bacteria. Analgesics such as phenazopyridine can be prescribed to relieve discomfort associated with UTIs. Estrogen therapy has also been suggested as a potential treatment option for UTIs, particularly in postmenopausal women. Trimethoprim-sulfamethoxazole or trimethoprim is recommended as first-line therapy for uncomplicated UTIs. The choice of drug and therapy for UTIs depends on the severity of the infection, the causative organism, and the presence of antibiotic resistance.Preventive measures encompass pre-transplant evaluation, perioperative strategies, post-transplant follow-up, and vaccination. A multidisciplinary approach involving transplant specialists, infectious disease experts, pharmacists, and patient engagement is vital for successful care. The future of UTI management lies in ongoing research, exploring personalized medicine, novel therapies, and innovative prevention strategies. By implementing these strategies and advancing research, healthcare providers can improve graft and patient survival, enhancing the quality of care for renal transplant recipients.

The emotional impact of uncomplicated urinary tract infections in women in China and Japan: a qualitative study

BackgroundUncomplicated urinary tract infections (uUTIs) are one of the most common community-acquired infections, particularly among women. Common symptoms of UTI include dysuria, urinary urgency and increased frequency, and lower abdominal pain. With appropriate treatment, symptoms may resolve in a few days. However, there is a lack of research on the emotional impact of this disease. We conducted a qualitative, interview-based study to gain a greater understanding of the emotional impact of uUTIs in women in China and Japan.MethodsA qualitative, exploratory, in-depth, interview-based study was conducted between 19 November 2020 and 25 February 2021. Women aged ≥ 18 years who experienced ≥ 1 uUTI and received antibiotic treatment in the past year were eligible for inclusion. Participants must have experienced ≥ 1 of the following symptoms during a uUTI episode: urinary urgency, frequency, dysuria, or lower abdominal/suprapubic pain. Participants who reported back pain or fever (indicative of complicated UTI) were excluded. Participants with recurrent or sporadic UTIs were included, with specific screening criteria used to ensure capture of both groups. Following a screening call, a structured, in-depth telephone interview (~ 30 min in duration) was conducted by three female external moderators trained in qualitative interviewing, assisted by an interview guide. Interviews were analysed individually and thematically, with the results presented within the identified themes.ResultsA total of 65 women with uUTI completed the in-depth telephone interview: 40 (62%) from China and 25 (38%) from Japan. Participants reported that the symptoms of uUTI affected multiple aspects of their lives, and described feelings of embarrassment, frustration, guilt, dread, and loneliness associated with symptoms that interfered with relationships, work and daily activities, and sleep. Participants reported seeking healthcare from several different points of contact, from local pharmacies to hospitals.ConclusionsOur analysis highlights the profound emotional impact of uUTIs in women in China and Japan, and the journey these participants take before their initial interaction with a healthcare professional. These insights emphasise the need to better understand the full impact of uUTI, and the role of healthcare professionals in improved patient education and support.

High Fosfomycin Susceptibility in Escherichia Coli Recovered from Urine in Brazil

Urinary Tract Infections (UTIs) are widespread globally, with a notably higher incidence in women. In 2018, the European Medicines Agency (EMA) endorsed the use of fluoroquinolones for uncomplicated UTI treatment. Following this recommendation, several international agencies adopted similar guidelines. Consequently, older antimicrobial agents like fosfomycin emerged as primary treatment options for UTIs. In this context, our study aimed to evaluate the susceptibility of Escherichia coli strains from urine samples to various recommended UTI antibiotics. These strains were collected between January 2017 and July 2020 in São Paulo, Brazil. We utilized the disk-diffusion method for antimicrobial susceptibility testing, interpreting the results according to BRCAST/EUCAST guidelines. Out of the 86,957 urine cultures undertaken during this timeframe, 10,041 yielded E. coli isolates. Of these, 8,655 were tested against fosfomycin, with 99.0% (8,572 strains) found to be susceptible. Additionally, susceptibility rates for other drugs were as follows: nitrofurantoin (95.8%), amoxicillin/clavulanic acid (83.9%), ciprofloxacin (65.1%), norfloxacin (65.6%), and levofloxacin (67.7%). Notably, of the 571 ESBL-positive strains, 94.0% were susceptible to fosfomycin. It’s important to mention a slight decline in fosfomycin susceptibility observed during this period. This finding underscores the importance of continuous monitoring for fosfomycin resistance and rational usage of the drug.

Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials

Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and a unique binding site, providing well balanced inhibition of two type II topoisomerase enzymes. Oral gepotidacin is under investigation to treat uncomplicated urinary tract infections. We aimed to compare the efficacy and safety of oral gepotidacin with that of nitrofurantoin in adolescent and adult female individuals with uncomplicated urinary tract infections. EAGLE-2 and EAGLE-3 were phase 3, randomised, multicentre, double-blind, double-dummy, non-inferiority (10% margin) trials, in which patients were enrolled at 219 centres worldwide. Patients assigned female at birth, non-pregnant, aged 12 years or older, weighing 40 kg or more, with two or more symptoms of dysuria, frequency, urgency, or lower abdominal pain, and with evidence of urinary nitrite, pyuria, or both were eligible for inclusion. Patients were randomly assigned (1:1) centrally by interactive response technology to receive oral gepotidacin (1500 mg twice daily for 5 days) or oral nitrofurantoin (100 mg twice daily for 5 days), with randomisation stratified by age category and history of recurrent uncomplicated urinary tract infections. Patients, investigators, and the sponsor study team were masked to treatment assignment. The primary endpoint, therapeutic response (success or failure) at test-of-cure (ie, day 10-13), was evaluated in randomly assigned patients with nitrofurantoin-susceptible qualifying uropathogens (≥105 colony-forming units [CFU] per mL) and who received at least one dose of study treatment. Conforming to regulatory guidance, therapeutic success was defined as combined clinical success (ie, complete symptom resolution) and microbiological success (ie, reduction of qualifying uropathogens to <103 CFU/mL) without other systemic antimicrobial use. Safety analyses included patients who were randomly assigned and who received at least one dose of study treatment. The trials are registered with ClinicalTrials.gov, NCT04020341 (EAGLE-2) and NCT04187144 (EAGLE-3), and are completed. Studies were undertaken from Oct 17, 2019, to Nov 30, 2022 (EAGLE-2), and from April 23, 2020, to Dec 1, 2022 (EAGLE-3). 1680 patients in EAGLE-2 and 1731 patients in EAGLE-3 were screened for eligibility, of whom 1531 and 1605 were randomly assigned, respectively (767 in the gepotidacin group and 764 in the nitrofurantoin group in EAGLE-2, and 805 in the gepotidacin group and 800 in the nitrofurantoin group in EAGLE-3). After an interim analysis, which was prospectively agreed as a protocol amendment, both studies were stopped for efficacy. Thus, the primary analysis population included only patients who, at the time of the interim analysis data cutoff, had the opportunity to reach the test-of-cure visit or were known to not have attained therapeutic success before the test-of-cure visit. In EAGLE-2, 162 (50·6%) of 320 patients assigned gepotidacin and 135 (47·0%) of 287 patients assigned nitrofurantoin had therapeutic success (adjusted difference 4·3%, 95% CI -3·6 to 12·1). In EAGLE-3, 162 (58·5%) of 277 patients assigned gepotidacin and 115 (43·6%) of 264 patients assigned nitrofurantoin had therapeutic success (adjusted difference 14·6%, 95% CI 6·4 to 22·8). Gepotidacin was non-inferior to nitrofurantoin in both studies and superior to nitrofurantoin in EAGLE-3. The most common adverse event with gepotidacin was diarrhoea (observed in 111 [14%] of 766 patients in EAGLE-2 and in 147 [18%] of 804 patients in EAGLE-3), whereas the most common adverse event with nitrofurantoin was nausea (in 29 [4%] of 760 patients in EAGLE-2 and in 35 [4%] of 798 patients in EAGLE-3). Cases were mostly mild or moderate. No life-threatening or fatal events occurred. Gepotidacin is an efficacious oral antibiotic with acceptable safety and tolerability profiles. As a first-in-class investigational oral antibiotic with activity against common uropathogens, including clinically important drug-resistant phenotypes, gepotidacin has the potential to offer substantial benefit to patients. GSK and the US Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority.

Gepotidacin, a new first-in-class antibiotic for treating uncomplicated urinary tract infection

Gepotidacin, a new first-in-class antibiotic for treating uncomplicated urinary tract infection

Urinary tract infection in pediatric patients – Recent updates

In children, urinary tract infection (UTI) is a common condition. Prompt identification and treatment are critical for reducing morbidity associated with this illness. Throughout infancy, the symptoms and indications remain nonspecific. During the first 2 years of life, the most prevalent sign of UTI is unexplained fever. Symptoms and indicators of pyelonephritis after the 2nd year of life include fever, chills, rigor, flank discomfort, and costovertebral angle tenderness. Suprapubic pain, dysuria, urinary frequency, urgency, murky urine, malodourous urine, and suprapubic tenderness are examples of the lower tract symptoms and indicators. When UTI is suspected, a urinalysis and urine culture should be conducted. In the treatment of acute uncomplicated UTI, second or third-generation cephalosporin and amoxicillin-clavulanate are currently the medications of choice. Parenteral antibiotic therapy is advised for infants under 2 months of age and any child who seems toxic is hemodynamically unstable, is immunocompromised, is unable to tolerate, or is not responding to oral medication. This study focuses on the most recent updates about UTIs in children and provides a comprehensive overview of the subject.

Intravaginal Delivery of Herbal Pharmaceutical Interventions for Uncomplicated UTIs in Women

Background: Urinary tract infection (UTIs) is the most common infection in women affecting approximately 75% of women worldwide during their pregnancy, and in pre and postmenopausal women. Typical symptoms include urinary frequency, urgency, suprapubic discomfort, and dysuria. Method: An introduction to the epidemiology of UTIs and detailed herbal nanoformulation treatment approach through novel intravaginal route is intended through this narrative review. UTIs are associated with significant morbidity and mortality, and they affect the quality of life of the affected patients. Multidrug-resistant bacteria and recurrent UTIs are becoming more common. Development of resistance, adverse effects of antibiotics, and other associated problems lead to establishing the research framework to find out the alternative approaches in controlling UTIs. Antibiotic- free treatments for uncomplicated urinary tract infections UTIs should be used, saving drugs for severe infections. Herbal medication might be used instead of antibiotics for uncomplicated UTIs, in addition to analgesics for purely symptomatic treatment. Conclusion: This review identifies the pathophysiology of UTI, distinguish the intravaginal route as an alternative to oral delivery route, summarizes the management of urinary tract infections and highlights the anti-uropathogenic and anti-bactericidal effects of herbal approaches to prevent or treat urinary tract infections.