Uncomplicated Uncomplicated Urinary Tract Infection 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.

Resistance to first-line antibiotic therapy among patients with uncomplicated acute cystitis in Melbourne, Australia: prevalence, predictors and clinical impact.

Australian guidelines recommend trimethoprim or nitrofurantoin as first-line agents for uncomplicated urinary tract infections (UTIs). Laboratory surveillance indicates high rates of trimethoprim resistance among urinary bacterial isolates, but there are scant local clinical data about risk factors and impact of trimethoprim resistance. To determine the prevalence, risk factors, mechanism and impact of resistance to first-line antibiotic therapy for uncomplicated UTIs in the community setting. A prospective observational study from October 2019 to November 2021 in four general practices in Melbourne, Australia. Female adult patients prescribed an antibiotic for suspected or confirmed uncomplicated acute cystitis were eligible. Primary outcome was urine isolates with resistance to trimethoprim and/or nitrofurantoin. We recruited 87 participants across 102 UTI episodes with median (IQR) age of 63 (47-76) years. Escherichia coli was the most common uropathogen cultured (48/62; 77%); 27% (13/48) were resistant to trimethoprim (mediated by a dfrA gene) and none were resistant to nitrofurantoin. Isolates with resistance to a first-line therapy were more common among patients reporting a history of recurrent UTIs [risk ratio (RR): 2.08 (95% CI: 1.24-3.51)] and antibiotic use in the previous 6 months [RR: 1.89 (95% CI: 1.36-2.62)]. Uropathogen resistance to empirical therapy was not associated with worse clinical outcomes. Resistance to trimethoprim is common in uncomplicated UTIs in Australia but may not impact clinical outcomes. Further research is warranted on the appropriateness of trimethoprim as empirical therapy, particularly for patients with antimicrobial resistance risk factors.

O02 Nitrofurantoin: what is the evidence for current guidance?

Abstract In this abstract, we review current approaches to the management of uncomplicated urinary tract infection (UTI) and begin to explore alternative approaches to antibiotic prescribing. We review clinical guidelines on the use of nitrofurantoin internationally to capture the level of variation in evidence-based guidance. We find that the evidence base has been interpreted in very different ways. UK guidelines from NICE and the Scottish Intercollegiate Guidelines Network (SIGN) are unusual in promoting short (3 day) courses of nitrofurantoin. We find little direct evidence to support this, and that this guidance has been extrapolated from studies based on other agents. ‘Short’ courses of antibiotics aim to provide optimum balance between providing effective treatment whilst reducing selective pressure driving resistance amongst colonizing microbial flora. Three days of nitrofurantoin may indeed be a useful intervention in a large group of patients. Longer courses of nitrofurantoin still demonstrate considerable rates of treatment failure. The concept of a course length in itself is limited. The variation between recommendations internationally reflects both the uncertain foundations upon which evidence-based guidelines are written, and the limits of what can be safely concluded from evidence. We join others in pointing out there may be ways of customizing duration of therapy to the patient’s response in primary care settings. There is a need for a more patient-focused approach to uncomplicated UTI, including better safety-netting and (currently lacking) guidance on best practice in the common clinical scenario of treatment failure.

Antibiotic treatment failure of uncomplicated urinary tract infections in primary care

BackgroundHigher resistance rates of > 20% have been noted in Enterobacteriaceae urinary isolates towards ciprofloxacin and co-trimoxazole (C + C) in Singapore, compared with amoxicillin-clavulanate and nitrofurantoin (AC + N). This study examined if treatment failure varied between different antibiotics, given different resistant rates, for uncomplicated urinary tract infections (UTIs) managed in primary care. We also aimed to identify gaps for improvement in diagnosis, investigations, and management.MethodsA retrospective cohort study was conducted from 2019 to 2021 on female patients aged 18–50 with uncomplicated UTIs at 6 primary care clinics in Singapore. ORENUC classification was used to exclude complicated UTIs. Patients with uncomplicated UTIs empirically treated with amoxicillin-clavulanate, nitrofurantoin, ciprofloxacin or co-trimoxazole were followed-up for 28 days. Treatment failure was defined as re-attendance for symptoms and antibiotic re-prescription, or hospitalisation for UTI complications. After 2:1 propensity score matching in each group, modified Poisson regression and Cox proportional hazard regression accounting for matched data were used to determine risk and time to treatment failure.Results3194 of 4253 (75.1%) UTIs seen were uncomplicated, of which only 26% were diagnosed clinically. Urine cultures were conducted for 1094 (34.3%) uncomplicated UTIs, of which only 410 (37.5%) had bacterial growth. The most common organism found to cause uncomplicated UTIs was Escherichia coli (64.6%), with 92.6% and 99.4% of isolates sensitive to amoxicillin-clavulanate and nitrofurantoin respectively. Treatment failure occurred in 146 patients (4.57%). Among 1894 patients treated with AC + N matched to 947 patients treated with C + C, patients treated with C + C were 50% more likely to fail treatment (RR 1.49, 95% CI 1.10–2.01), with significantly higher risk of experiencing shorter time to failure (HR 1.61, 95% CI 1.12–2.33), compared to patients treated with AC + N.ConclusionTreatment failure rate was lower for antibiotics with lower reported resistance rates (AC + N). We recommend treating uncomplicated UTIs in Singapore with amoxicillin-clavulanate or nitrofurantoin, based on current local antibiograms. Diagnosis, investigations and management of UTIs remained sub-optimal. Future studies should be based on updating antibiograms, highlighting its importance in guideline development.

Patient-reported outcome measures for uncomplicated urinary tract infections in women: a systematic review

PurposeTo conduct a systematic review of the quality of existing patient-reported outcome measures (PROMs) for use in women with uncomplicated urinary tract infections (UTIs) applying the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology, and to derive recommendations for their use in future research.MethodsA systematic literature search was performed in PubMed and Web of Science. Studies reporting on the development and/or validation of any PROMs for uncomplicated UTIs in women were considered eligible. We evaluated the methodological quality of each included study using the COSMIN Risk of Bias Checklist, and further applied predefined criteria for good measurement properties. Finally, we graded the evidence and derived recommendations for the use of the included PROMs.ResultsData from 23 studies reporting on six PROMs were included. From those, the Acute Cystitis Symptom Score (ACSS) and the Urinary Tract Infection-Symptom and Impairment Questionnaire (UTI-SIQ-8) can be recommended for further use. Both instruments showed sufficient content validity. We further found high-quality evidence for sufficient internal consistency of the UTI-SIQ-8, while this criterion was not assessed for the ACSS due to a formative measurement model. All other PROMs have the potential to be recommended for use, but require further validation.ConclusionThe ACSS and the UTI-SIQ-8 have the potential to be recommended for use in women with uncomplicated UTIs in future clinical trials. For all included PROMs, further validation studies are indicated.Systematic review registration: PROSPERO.

COSUTI: A Core Outcome Set (COS) for Interventions for the Treatment of Uncomplicated Urinary Tract Infection (UTI) in Adults.

Background: Uncomplicated urinary tract infections (UTIs) are among the most common presentations of bacterial infections in the outpatient setting. The variation of outcomes reported in trials to assess the most effective treatment interventions for uncomplicated UTIs has meant that comparing and synthesising the outcomes across trials is challenging and limits the reliability of evidence which would otherwise inform healthcare decisions. Objective: Develop a Core Outcome Set (COS) for interventions for the treatment of uncomplicated UTIs in otherwise healthy adults. Methods: The COS development consisted of three phases: (1) A systematic review to identify outcomes reported in randomised trials and systematic reviews of randomised trials comparing the effectiveness of any interventions for the treatment of uncomplicated UTI in otherwise healthy adults; (2) Outcomes identified in the systematic review were prioritised in an online 3-round modified Delphi survey with healthcare practitioners (n = 68), researchers (n = 5), and people who have experienced or cared for someone experiencing a UTI (n = 180); (3) An online consensus meeting to determine the final COS with healthcare practitioners and policymakers (n = 9), researchers (n = 4), and people who have experienced or cared for someone experiencing a UTI (n = 7). Results: We identified a large number of outcomes. Through the use of robust consensus methods, those outcomes were reduced to a core set of six outcomes that should, at a minimum, be measured and reported in randomised trials and systematic reviews of interventions treating uncomplicated UTIs in adults.

Revisiting β-Lactams for Treatment of Urinary Tract Infections: Assessing Clinical Outcomes of Twice-Daily Cephalexin for Empiric Treatment of Uncomplicated Urinary Tract Infections.

The 2011 Infectious Diseases Society of America guidelines for treatment of uncomplicated urinary tract infections (UTIs) recommend non-β-lactam antibiotics for empiric therapy. However, increasing Escherichia coli and Klebsiella spp. resistance to first-line antibiotic therapies has necessitated the need for alternative agents. Based on local antibiogram data, cephalexin has become the preferred oral antibiotic for empiric treatment of UTIs at our institution. The purpose of this single-center retrospective review was to assess clinical outcomes of patients discharged from the emergency department (ED) who received cephalexin for the treatment of uncomplicated UTIs. The primary outcome of this study was to assess the proportion of patients with clinical success 30 days after discharge from the ED. Patients were excluded if they were <18 years of age, received ≥10 days of cephalexin, received antibiotics for any indication other than uncomplicated UTI, received antibiotics within 60 days of their ED visit, or had structural abnormalities. A total of 264 patients were included for evaluation, and 214 patients (81.1%) met the criteria for clinical success. Overall, 28 (10.6%) patients required a change in antibiotics based on cultures and sensitivities, 18 (6.8%) patients returned for nonresolving or worsening symptoms, and 4 (1.5%) patients required both a change in antibiotics and returned for nonresolving or worsening symptoms. Short courses of twice-daily cephalexin appear to be a safe and effective option for the empiric treatment of uncomplicated UTIs.

Compliance to Guidelines in Prescribing Empirical Antibiotics for Individuals with Uncomplicated Urinary Tract Infection in a Primary Health Facility of Ghana, 2019-2021.

Increasing trends in antimicrobial resistance among uropathogens call for rational use of empirical antibiotics for managing uncomplicated urinary tract infections (UTIs). In Ghana, standard treatment guidelines (STGs) for UTI recommend oral ciprofloxacin or cefuroxime for 5–7 days in females and 10–14 days in males. We conducted a cross-sectional audit using electronic medical records (EMR) to assess compliance to the STGs among adults (≥18 years) with uncomplicated UTIs diagnosed in a primary health facility between October 2019 and October 2021. Among 3717 patients, 71% were females and all had complete prescription details in the EMR. Of all the patients, 83% were prescribed empirical antibiotics, of whom 88% received oral ciprofloxacin or cefuroxime. Only 68% were prescribed antibiotics for the correct duration, which was significantly lower among males (10%) compared to females (90%). Among patients who received antibiotics, 60% were prescribed in line with the STGs. The results call for feedback to physicians about poor compliance to STGs with duration of antibiotic prescribed. Recommendations on 10–14 days duration of antibiotics for males needs to be reassessed and necessary amendments to STGs can be made. Leveraging the well-established EMR system, a real-time audit-feedback mechanism can be instituted to improve compliance with STGs.

In vitro activity of nitroxoline against carbapenem-resistant Acinetobacter baumannii isolated from the urinary tract

The old antimicrobial nitroxoline is currently repurposed for oral treatment of uncomplicated urinary tract infections (UTIs). To investigate the in vitro activity of nitroxoline against carbapenem-resistant Acinetobacter baumannii (CRAb). From an international collection of previously well-characterized clinical A. baumannii isolates, 34 isolates from urinary tract sources with different carbapenem-resistance mechanisms were selected. Nitroxoline activity was analysed with broth microdilution (BMD), disc diffusion (DD) and within an in vitro biofilm model. MICs of meropenem and imipenem were assessed with BMD. Susceptibility to ciprofloxacin and trimethoprim/sulfamethoxazole was investigated using DD. Escherichia coli ATCC 25922 and A. baumannii NCTC 13304 were used for quality control. All isolates were carbapenem resistant (MIC90 >32 mg/L for meropenem and imipenem) and most isolates were resistant to ciprofloxacin (33/34) and trimethoprim/sulfamethoxazole (31/34). Nitroxoline yielded MIC50/90 values of 2/2 mg/L (MIC range 1-2 mg/L) and inhibition zone diameters ranging from 20 to 26 mm. In contrast, for definite eradication of biofilm-associated CRAb in vitro, higher nitroxoline concentrations (≥16 to ≥128 mg/L) were necessary for all isolates. Nitroxoline showed excellent in vitro activity against a collection of CRAb despite high resistance rates to other antimicrobials for parental and oral therapy of A. baumannii UTI. Currently, nitroxoline is recommended for the treatment of uncomplicated UTI in Germany with a EUCAST breakpoint limited to uncomplicated UTI and E. coli (S ≤16 mg/L). Nitroxoline could be a promising drug for oral treatment of lower UTI caused by CRAb. More data are warranted to correlate these findings with in vivo success rates.

Incidence of urosepsis or pyelonephritis after uncomplicated urinary tract infection in older women.

Our primary aim was to describe the incidence of the diagnosis of urosepsis or pyelonephritis during the 60 days following initial evaluation of an uncomplicated urinary tract infection (UTI) among female Medicare beneficiaries ≥ 65 years of age. This was a retrospective cohort study of women ≥ 65 years of age undergoing evaluation for an incident, uncomplicated urinary tract infection (UTI) between the years 2011-2018 included in the Medicare 5% Limited Data Set (LDS). We grouped women into age categories of 65-74 years, 75-84 years, or > 84 years old. We excluded women with possible complicated UTI, those hospitalized within 60 days prior to index UTI evaluation, and those residing in a nursing home and place of service consistent with an inpatient setting/facility. The association between age and risk of each outcome was estimated with Cox proportional hazards models, controlling for relevant comorbidities. Between 2011-2018, 169,958 women met our inclusion/exclusion criteria and were evaluated for uncomplicated UTI. In total, 2935 (1.7%) had a subsequent diagnosis of either urosepsis (n = 2848, 1.6%) or pyelonephritis (n = 145, 0.08%). In adjusted analysis, the hazard of urosepsis was significantly higher for women > 84 years (aHR 1.49, 95% CI 1.38, 1.65; p < 0.01) and those aged 75-84 (aHR 1.24, 95% CI 1.13, 1.37; p < 0.01) compared to those aged 65-74 years. In contrast, age group was not significantly associated with the hazard for pyelonephritis. Urosepsis and pyelonephritis are very uncommon after evaluation of incident uncomplicated UTI in female medical beneficiaries ≥ 65 years of age.

Antibiotic resistance in patients with urinary tract infections in Pakistan.

The level of antibiotic resistance of pathogens causing uncomplicated urinary tract infections (UTIs) is increasing. The 2017-2018 GLASS (Global Antimicrobial Resistance and Use Surveillance System) report indicated >70% resistance to ceftriaxone and ciprofloxacin in Escherichia coli in Pakistan. A prospective study was conducted in the Médecins Sans Frontières (MSF) supported Timurgara District Hospital, Timurgara, Pakistan, from September 2017 to December 2018. Women aged 18-65 years presenting to the Emergency Department with symptoms of uncomplicated UTI (cystitis/pyelonephritis) were invited to participate. We conducted microbiological culture and sensitivity testing for samples with positive dipstick or nitrite test. Of the 200 patients who participated, 109 (54.5%) were diagnosed with pyelonephritis and 91 (45.5%) with cystitis. Forty-three samples (21.5%) were culture-positive: E. coli was isolated in 27 samples, Enterococcus spp. in 7 and Klebsiella pneumoniae in 6. Overall resistance to ciprofloxacin was observed in 51.8% of E. coli isolates, and ceftriaxone resistance in 66.7% of E. coli isolates and in 33.3% of K. pneumoniae. Resistance to fosfomycin was low (one E. coli isolate). This study found resistance to first- and second-line antibiotics for treating UTIs as per the MSF protocol. Heightened awareness and potential changes to local prescription practices are necessary to curb the spread of antimicrobial resistance pathogens causing UTIs.

Hausärztliche Perspektiven auf eine multimodale Intervention zum adäquaten Einsatz von Antibiotika beim Harnwegsinfekt – eine qualitative Interviewstudie

IntroductionContrary to current guideline recommendations, second-line antibiotics are still frequently used in the ambulatory treatment of uncomplicated urinary tract infections (UTI), which are associated with a high risk of antibiotic resistance development. The REDARES project (REDuction of Antibiotic RESistance in uncomplicated urinary tract infections by treatment according to national guidelines in ambulatory care), funded by the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA)/Innovation Fund is developing a multimodal intervention for primary care physicians to support them in a guideline-based approach. The intervention consists of the following components: (1) provision of local resistance data of pathogens of uncomplicated UTI (Robert Koch Institute), (2) concise guideline content on the therapy of uncomplicated UTI for patients (paper and online), and (3) prescription feedback on practice level and benchmarking among the study participants (anonymized). In a participatory approach and as part of the process evaluation, representatives of the intended target group were interviewed in advance about the acceptance and feasibility of the intervention. MethodsUsing guided individual interviews, Thuringian GPs were interviewed before the start of the intervention phase. Following a description of the study concept and the planned components of the intervention, the interviewees were asked about their assessment regarding acceptance and feasibility. The individual interviews were recorded, transcribed verbatim and qualitatively analyzed according to Mayring. ResultsA total of ten interviews with an average duration of 29minutes were conducted and evaluated. 40 per cent of the interviewed GPs were female and, on average, 45 years old. The interviewees described the uncomplicated UTI as an easily manageable condition. The practical nature of the research question was described as a reason to potentially participate in the intervention phase; lack of time or human resources were cited as potential barriers. Regarding the intervention elements, the provision of local resistance data of UTI pathogens was considered beneficial to their own work. The extraction of their own antibiotic prescription data from the practice software was basically assessed as feasible. The interviewees differed in their assessment of whether they would take account of the feedback on their prescribing behavior in their daily work. DiscussionThe interviews generated a detailed picture of the different diagnostic and therapeutic pathways used by respondents for uncomplicated UTI. Overall, they predominantly regarded both the study concept and the intervention components as feasible. Although the study population is small and not representative, some of the results seem to be transferable to other regions in Germany. ConclusionA research question relating to their daily routine can increase participation of primary care physicians in (intervention) studies. Starting the process evaluation before the intervention seems to be reasonable since the results will be integrated into the design of the intervention. The method of data extraction from practice software by practice teams seems to be promising.

Whole-Person, Urobiome-Centric Therapy for Uncomplicated Urinary Tract Infection.

A healthy urinary tract contains a variety of microbes resulting in a diverse urobiome. Urobiome dysbiosis, defined as an imbalance in the microbial composition in the microenvironments along the urinary tract, is found in women with uncomplicated urinary tract infection (UTI). Historically, antibiotics have been used to address UTI. An alternative approach to uncomplicated UTI is warranted as the current paradigm fails to take urobiome dysbiosis into account and contributes to the communal problem of resistance. A whole-person, multi-modal approach that addresses vaginal and urinary tract dysbiosis may be more effective in reducing recurrent UTI. In this review, we discuss strategies that include reducing pathogenic bacteria while supporting commensal urogenital bacteria, encouraging diuresis, maintaining optimal pH levels, and reducing inflammation. Strategies for future research are suggested.

Urinary manifestations in African American and Caucasian inflammatory bowel disease patients: a retrospective cohort study

BackgroundInflammatory bowel diseases (IBD), like ulcerative colitis (UC) and Crohn’s disease (CD), are associated with urinary extra-intestinal manifestations, like urolithiasis and uncomplicated urinary tract infections (UTIs). The literature reviewed for this study identifies an increased association of CD and urolithiasis against the general population as well as UC. Furthermore, the rates in which urinary comorbidities manifest have not been well characterized in cross-race analyses. The purpose of this study is to establish the prevalence of common urinary extra-intestinal manifestations in CD and UC and to further determine at what rate these affect the African American and Caucasian populations.MethodologyThis is a retrospective cohort study using de-identified data collected from a research data base that included 6 integrated facilities associated with one tertiary healthcare center from 2012 to 2019. The electronic chart records for 3104 Caucasian and African American IBD patients were reviewed for frequency of urolithiasis and uncomplicated UTI via diagnosed ICD-10 codes. Comparison between data groups was made using multivariate regressions, t-tests, and chi square tests.ResultsOur study included 3104 patients of which 59% were female, 38% were African American, and 43% were diagnosed with UC. Similar proportions of UC and CD diagnosed patients developed urolithiasis (6.0% vs 6.7%, p = 0.46), as well as uncomplicated UTIs (15.6% vs. 14.9%, p = 0.56). Similar proportions of African American and Caucasian patients developed urolithiasis (5.4% vs 7.0%, p = 0.09), but a higher proportion of African Americans developed uncomplicated UTIs (19.4% vs 12.6%, p ≤ 0.001).ConclusionWe found similar rates of urolithiasis formation in both UC and CD in this study. Furthermore, these rates were not significantly different between African American and Caucasian IBD populations. This suggests that UC patients have an elevated risk of urolithiasis formation as those patients with CD. Additionally, African Americans with IBD have a higher frequency of uncomplicated UTI as compared to their Caucasian counterparts.

Assessment of Drug Sensitivity of Different Urinary Isolates to Nitrofurantoin and its Comparison with Other DrugsA Retrospective Study

Introduction: Uncomplicated Urinary Tract Infection (UTI) is one of the most common indications for antibiotic use in the community. However, gram negative organisms that are predominant cause of UTI are becoming increasingly resistant to commonly used antibiotics. Consequently, empiric therapy is likely to fail resulting in increasing number of patients with uncomplicated UTI requiring hospitalisation for intravenous antibiotics as there are no oral treatment options left. Aim: To assess the susceptibility trends of urinary isolates to panel of antibiotics with particular reference to nitrofurantoin. Materials and Methods: The present study was a retrospective study conducted at Adesh Hospital Bathinda, Punjab, India for a period of one year from April 2020-April 2021. Kass criteria was followed for interpretation of significant bacteriuria according to which significant growth is considered if number of colony is more than 105 Colony Forming Unit (CFU)/mL. Culture positive were analysed by Gram staining and on the basis of colony characteristics, gram staining, final identification was done using Vitek 2 compact system. Statistical analysis was done using Chi-square test. Results: A total of 392 urinary isolates were identified during the study period. Out of the 392 isolates 316 (80.6%) were gram negative isolates and 76 (19.4%) were gram positive isolates. Maximum sensitivity was shown to nitrofurantoin, 88% in case of gram negative isolates and 76% in case of gram positive isolates. Conclusion: Nitrofurantoin is an effective therapeutic agent in the treatment of UTI. It has been used for a long time, but the emergence of antibiotic resistance and the decline in newly developed antibiotics has increased interest in the treatment of bacterial UTI with this antibiotic

Efficacy and safety of quinolones vs. other antimicrobials for the treatment of uncomplicated urinary tract infections in adults: a systematic review and meta-analysis.

In the present study, we aimed to compare the efficacy and safety of quinolones with trimethoprim-sulfamethoxazole (TMP/SMX), nitrofurantoin, fosfomycin, and β-lactams for the treatment of uncomplicated urinary tract infections (UTIs) in adults. All controlled clinical trials assessing quinolones for uncomplicated UTIs in adults were searched from PubMed, Embase, and Cochrane Library databases. Meta-analyses were used to evaluate the efficacy and safety in randomized controlled trials (RCTs). A total of 47 RCTs consisting of 8992 patients were included in the present analysis. The clinical and bacteriological remission rates of quinolones were significantly higher (P < 0.01) compared with β-lactams and nitrofurantoin, while quinolones showed similar clinical and bacteriological remission rates compared with TMP/SMX and fosfomycin. Moreover, the bacterial resistance and relapse rates of quinolones were significantly lower (P < 0.01) compared with TMP/SMX, β-lactams, and nitrofurantoin. Regarding the adverse drug reactions (ADRs), quinolones did not bring higher risks, while the incidence of ADRs in the quinolone group was also even significantly lower (P < 0.01) compared with the TMP/SMX and nitrofurantoin groups, including the most reported ADRs associated with the gastrointestinal tract. Compared with other anti-UTI drugs, quinolones exerted an excellent effect on clinical remission and bacteriological eradication, and the application of quinolones did not bring a higher risk of ADRs.

Association of Adverse Events With Antibiotic Treatment for Urinary Tract Infection.

Little is known about the relative harms of different antibiotic regimens prescribed to treat uncomplicated urinary tract infection (UTI). We sought to compare the risk of adverse events associated with commonly used oral antibiotic regimens for the outpatient treatment of uncomplicated UTI. Using data from the IBM® MarketScan® Commercial Database, we identified 1 169 033 otherwise healthy, nonpregnant women aged 18-44 years with uncomplicated UTI who initiated an oral antibiotic with activity against common uropathogens from 1 July 2006 to 30 September 2015. We used propensity score-weighted Kaplan-Meier methods and Cox proportional hazards regression models to estimate the association between antibiotic agent and adverse events. Of 2 first-line agents, trimethoprim-sulfamethoxazole (vs nitrofurantoin) was associated with higher risk of several adverse drug events including hypersensitivity reaction (hazard ratio, 2.62; 95% confidence interval, 2.30-2.98), acute renal failure (2.56; 1.55-4.25), skin rash (2.42; 2.13-2.75), urticaria (1.37; 1.19-1.57), abdominal pain (1.14; 1.09-1.19), and nausea/vomiting (1.18; 1.10-1.28), but a similar risk of potential microbiome-related adverse events. Compared with nitrofurantoin, non-first-line agents were associated with higher risk of several adverse drug events and potential microbiome-related adverse events including non-Clostridium difficile diarrhea, C. difficile infection, vaginitis/vulvovaginal candidiasis, and pneumonia. Treatment duration modified the risk of potential microbiome-related adverse events. The risks of adverse drug events and potential microbiome-related events differ widely by antibiotic agent and duration. These findings underscore the utility of using real-world data to fill evidentiary gaps related to antibiotic safety.

Herbal treatment with uva ursi extract versus fosfomycin in women with uncomplicated urinary tract infection in primary care: a randomized controlled trial

ObjectiveWe explored whether initial treatment with the herbal drug uva ursi (UU) reduces antibiotic use in women with uncomplicated urinary tract infection (UTI) without increasing symptom burden and complication frequency compared with antibiotic treatment. MethodsA double-blind randomized controlled trial was conducted in 42 family practices in Germany. The participants were adult women with suspected uncomplicated UTIs receiving either UU 105 mg 3 × 2 tablets for 5 days (intervention) or fosfomycin a 3-g single dose (control), and their respective placebos. Participants and investigators were blinded. The primary outcome included (1) antibiotic courses day 0–28 as superiority, and (2) symptom burden (sum of daily symptom scores) day 0–7, as non-inferiority outcome (margin 125%). Clinicaltrials.gov: NCT03151603. ResultsOverall, 398 patients were randomly allocated to groups receiving UU (n = 207) and fosfomycin (n = 191). The number of antibiotic courses was 63.6% lower (95% CI 53.6%–71.4%; p < 0.0001) in the UU group than in the fosfomycin group. The ratio of total symptom burden in the UU group compared with control was 136.5% (95% CI 122.7–151.9; p 0.95), failing non-inferiority. Eight women developed pyelonephritis in the UU group compared with two in the fosfomycin group (mean difference 2.8; 95% CI 0.2–5.9; p 0.067). Adverse events were similar between the groups. DiscussionIn women with uncomplicated UTIs, initial treatment with UU reduced antibiotic use but led to a higher symptom burden and more safety concerns than fosfomycin.

Risk of antibiotic treatment failure in premenopausal women with uncomplicated urinary tract infection.

Acute uncomplicated urinary tract infections (UTIs) are among the most common indications for antibiotic prescriptions in otherwise healthy women. We compared the risk of treatment failure of antibiotic regimens for outpatient treatment of UTI in real-world practice. We identified non-pregnant, premenopausal women diagnosed with uncomplicated, lower tract UTI and prescribed an oral antibiotic with activity against common uropathogens. We used propensity score-weighted Kaplan-Meier functions to estimate 30-day risks and risk differences (RD) for pyelonephritis and UTI-related antibiotic prescription switch. Of 1 140 602 patients, the distribution of index prescriptions was 44% fluoroquinolones (non-first-line), 28% trimethoprim-sulfamethoxazole (TMP/SMX) (first-line), 24% nitrofurantoin (first-line), 3% narrow-spectrum β-lactams (non-first-line), 1% broad-spectrum β-lactams (non-first-line), and 1% amoxicillin/ampicillin (non-recommended). Compared to the risk of pyelonephritis for nitrofurantoin (0.3%), risks were higher for TMP/SMX (RD, 0.2%; 95% CI, 0.2%-0.2%) and broad-spectrum β-lactams (RD, 0.2%; 95% CI, 0.1%-0.4%). Compared to the risk of prescription switch for nitrofurantoin (12.7%), the risk was higher for TMP/SMX (RD 1.6%; 95% CI 1.3%-1.7%) but similar for broad-spectrum β-lactams (RD -0.7%; 95% CI -1.4%-0.1%) and narrow-spectrum β-lactams (RD -0.3%; 95% CI -0.8%-0.2%). Subgroup analyses suggest TMP/SMX treatment failure may be due in part to increasing uropathogen resistance over time. The risk of treatment failure differed by antibiotic agent, with higher risk associated with TMP/SMX versus nitrofurantoin, and lower or similar risk associated with broad- versus narrow-spectrum β-lactams. Given serious safety warnings for fluoroquinolones, these results suggest that nitrofurantoin may be preferable as the first-line agent for outpatient treatment of uncomplicated UTI.

Rural-urban differences in antibiotic prescribing for uncomplicated urinary tract infection.

To examine rural-urban differences in temporal trends and risk of inappropriate antibiotic use by agent and duration among women with uncomplicated urinary tract infection (UTI). Observational cohort study. Using the IBM MarketScan Commercial Database (2010-2015), we identified US commercially insured women aged 18-44 years coded for uncomplicated UTI and prescribed an oral antibiotic agent. We classified antibiotic agents and durations as appropriate versus inappropriate based on clinical guidelines. Rural-urban status was defined by residence in a metropolitan statistical area. We used modified Poisson regression to determine the association between rural-urban status and inappropriate antibiotic receipt, accounting for patient- and provider-level characteristics. We used multivariable logistic regression to estimate trends in antibiotic use by rural-urban status. Of 670,450 women with uncomplicated UTI, a large proportion received antibiotic prescriptions for inappropriate agents (46.7%) or durations (76.1%). Compared to urban women, rural women were more likely to receive prescriptions with inappropriately long durations (adjusted risk ratio 1.10, 95% CI, 1.10-1.10), which was consistent across subgroups. From 2011 to 2015, there was slight decline in the quarterly proportion of patients who received inappropriate agents (48.5% to 43.7%) and durations (78.3% to 73.4%). Rural-urban differences varied over time by agent (duration outcome only), geographic region, and provider specialty. Inappropriate antibiotic prescribing is quite common for the treatment of uncomplicated UTI. Rural women are more likely to receive inappropriately long antibiotic durations. Antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing and to reduce unnecessary exposure to antibiotics, particularly in rural settings.