Effect of methenamine hippurate shortage on antibiotic prescribing for urinary tract infections in Norway-an interrupted time series analysis.

BACKGROUND: Despite a lack of conclusive evidence of effect, methenamine hippurate is widely prescribed as preventive treatment for recurrent urinary tract infections (UTIs) in Norway. A national discontinuation of methenamine hippurate treatment due to a 4-month drug shortage in 2019 presented an opportunity to evaluate its preventive effect on UTIs among regular users. OBJECTIVE: To estimate the impact of the methenamine hippurate drug shortage on prescription frequency of UTI antibiotics. METHODS: Data from The Norwegian Prescription Database was analysed using an interrupted time series design. The time series consisted of 56 time periods of 14 days. The model included two naturally occurring interruptions: (i) the methenamine hippurate drug shortage, and (ii) reintroduction of the drug. The study population were 18 345 women ≥50 years receiving ≥2 prescriptions of methenamine hippurate in the study period before the shortage. Main outcome measure was number of prescriptions of UTI antibiotics per 1000 methenamine hippurate users. Prescription rates of antibiotics for respiratory tract infections were analysed to assess external events affecting antibiotic prescribing patterns. RESULTS: We found a significant increase of 2.41 prescriptions per 1000 methenamine hippurate users per 14-day period during the drug shortage (95%CI 1.39, 3.43, P < 0.001), followed by a significant reduction of -2.64 prescriptions after reintroduction (95%CI -3.66, -1.63, P < 0.001). CONCLUSIONS: During the methenamine hippurate drug shortage, we found a significant increase in prescribing trend for UTI antibiotics followed by a significant decrease in prescribing trend after reintroduction. This change in trend seems to reflect a preventive effect of the drug on recurrent UTIs.

Use of Methenamine for Urinary Tract Infection Prophylaxis: Systematic Review of Recent Evidence.

INTRODUCTION AND HYPOTHESIS: Antibiotic resistance is an unavoidable consequence of antibiotic use and growing rates of resistance are an urgent issue. Methenamine is a non-antibiotic alternative used for urinary tract infection (UTI) prophylaxis. The objective of this review is to evaluate recently published literature regarding the efficacy and safety of methenamine for UTI prophylaxis. METHODS: PubMed, Embase, and CENTRAL databases were queried in March 2023 using the following search terms: urinary tract infection, cystitis, bacteriuria, or dysuria, and methenamine. Studies prior to 2012 were excluded from this review to focus on appraisal of the most recent evidence. Prospective and controlled retrospective trials were included for review. RESULTS: A total of seven studies (three prospective and four retrospective) met the inclusion criteria for review. Two of the 3 prospective studies demonstrated no or non-inferior differences in clinical efficacy to prevent recurrent UTIs between methenamine and antibiotic prophylaxis and the third showed decreased rates of UTI with methenamine use in patients with short-term indwelling catheters compared with cranberry alone. The retrospective studies consistently supported the efficacy and safety of methenamine for UTI prophylaxis in a variety of populations and clinical settings. Adverse effects reported with methenamine were similar to comparators and included nausea, abdominal pain, and headache. CONCLUSIONS: The use of methenamine for UTI prophylaxis was shown to be effective in a variety of settings without an increased risk of adverse effects compared with prophylactic antibiotics. Larger blinded clinical trials are needed to further define the role of methenamine in UTI prophylaxis.

Evidence-based review of nonantibiotic urinary tract infection prevention strategies for women: a patient-centered approach.

PURPOSE OF REVIEW: There is a growing interest in nonantibiotic prevention strategies for recurrent urinary tract infections (rUTIs). Our objective is to provide a focused, pragmatic review of the latest evidence. RECENT FINDINGS: Vaginal estrogen is well tolerated and effective for preventing rUTI in postmenopausal women. Cranberry supplements at sufficient doses are effective in preventing uncomplicated rUTI. Methenamine, d -mannose, and increased hydration all have evidence to support their use, although the evidence is of somewhat variable quality. SUMMARY: There is sufficient evidence to recommend vaginal estrogen and cranberry as first-line rUTI prevention strategies, particularly in postmenopausal women. Prevention strategies can be used in series or in tandem, based on patient preference and tolerance for side effects, to create effective nonantibiotic rUTI prevention strategies.

The resurgence of methenamine hippurate in the prevention of recurrent UTIs in women- a systematic review.

PURPOSE OF REVIEW: Recurrent urinary tract infections (rUTIs) in women are prevalent and difficult to manage. The rise of antimicrobial resistance makes it prudent to re-investigate the role of nonantimicrobial agents in the prevention of RUTIs. We wanted to evaluate randomised controlled trials (RCTs) that employed methenamine hippurate as a therapy or prophylactic in adult women with rUTIs. RECENT FINDINGS: Relevant databases were searched for RCTs using Cochrane methodology and reporting items for systematic reviews and meta-analyses (PRISMA) checklist, comparing the efficacy of methenamine hippurate to either an antibiotic or a placebo for the prophylaxis of rUTI in women.Six trials involving 322 patients taking methenamine and 419 patients receiving antibiotics in total were evaluated. The duration of the trials ranged from 12-24 months. Studies reported that methenamine was effective in extending the mean period between symptomatic episodes of urinary tract infections (UTIs), keeping the patient symptom- and infection-free, and reducing the number of UTI episodes. The newer studies reported that methenamine reduced the incidence rates of recurrent UTIs and was not inferior to the antibiotic in this regard. SUMMARY: The outcomes of methenamine hippurate were found to be at par with the antibiotic prophylaxis. It might serve as a suitable alternative nonantibiotic prophylaxis for females with rUTIs.

Methenamine hippurate compared with trimethoprim for the prevention of recurrent urinary tract infections: a randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: The objective was to find an alternative treatment to a low-dose antibiotic for the prevention of recurrent urinary tract infections (UTI) and to evaluate the difference in rates of reinfection within 1 year when treated with methenamine hippurate for prophylaxis compared with trimethoprim. METHODS: We present a non-blinded randomized trial comparing methenamine hippurate with trimethoprim for the prevention of recurrent UTI at 12 months after starting treatment. Women over 18 who had at least two culture-positive UTI in the prior 6 months or three in the prior year were included. Ninety-two patients met enrollment criteria and were randomized to receive daily prophylaxis with methenamine hippurate or trimethoprim for a minimum of 6 months. Both intent-to-treat and per-protocol analyses if patients received the alternative drug after randomization were analyzed using Student's t test, Mann-Whitney U test, Kaplan-Meier curves, log-rank test, and a logistic and multivariate regression model. The primary outcome of this study was culture-proven UTI recurrence by 12 months after initiating prophylaxis. RESULTS: In the intent-to-treat analysis, we found no difference between groups in recurrent UTI, with a 65% (28 out of 43) recurrence in the trimethoprim group versus 65% (28 out of 43) in the methenamine hippurate group (p = 1.00). In the per-protocol analysis, 65% (26 out of 40) versus 65% (30 out of 46) of patients had UTI recurrences in the trimethoprim group versus the methenamine hippurate group (p = 0.98). CONCLUSIONS: Methenamine hippurate may be an alternative for the prevention of recurrent UTI, with similar rates of recurrence and adverse effects to trimethoprim.

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 pointsMethenamine 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.

Effectiveness of Methenamine for UTI Prevention in Older Adults.

Background: Methenamine is a drug used for the prevention of lower urinary tract infections (UTIs). However, efficacy has not been established in older adults or patients with varying degrees of kidney function. Objective: To evaluate the effectiveness of methenamine for the prevention of UTI in adults 60 years and older. Methods: This was a retrospective, pre-post, observational study. The study included primary care patients 60 years and older who were taking methenamine between January 1, 2015, and September 30, 2018. The primary outcome was the time to first UTI after methenamine initiation compared with the average time between UTIs in the 12 months prior to methenamine initiation. Results: Of 434 patients reviewed, 150 met inclusion criteria. The average time to UTI was 3.3 months prior to methenamine initiation compared with 5.5 months after methenamine initiation (P = 0.0004). There were 33 patients (22%) who did not have a UTI after methenamine initiation. Also, 14 patients (9.3%) had a calculated CrCl <30 mL/min at baseline. The average time to UTI in these patients was 3.3 months prior to methenamine initiation compared with 12.7 months after initiation (P < 0.0001). Conclusion and Relevance: Methenamine use was associated with a longer time to UTI in older adults with varying degrees of kidney function. The effectiveness of methenamine appeared to be similar regardless of kidney function, which is new evidence. Because of a lack of acquired resistance, methenamine may be an effective option for UTI prophylaxis in older adults.

Should I stay or should I go? A qualitative study exploring participation in a urology clinical trial.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to identify modifiable factors to improve recruitment in a urology clinical trial of women with recurrent urinary tract infection (rUTI). An embedded qualitative study was conducted with patients and recruiting clinicians in the first 8 months of the trial. We present a matrix of factors influencing how patients make decisions about trial participation. METHODS: This was a qualitative study using telephone interviews. When they were first approached about the trial, women were asked to complete an expression of interest form if they wished to be contacted for an interview. Data were analysed thematically. NVivo 10 software (Qualitative data analysis software. 10th ed: QSR International Pty Ltd; 2012) was used as a management tool. RESULTS: Thirty patients and 11 clinicians were interviewed. Influences on patient participation included the impact of rUTI on quality of life (QoL), understanding of antibiotic resistance, and previous experiences with antibiotics either positive or negative. Very few women who declined the trial agreed to be interviewed. However, some of those who participated had reservations about it. These included the perceived risk of trying a new treatment, trial length, and the burden of participating. One person interviewed left the trial because of repeated infections and difficulties getting general practitioner appointments. CONCLUSIONS: A combination of factors worked to influence women to decide to participate, to remain in, or to leave the trial. A better understanding of how these factors interact and work can assist in the recruitment and retention of individual trial participants.

Methenamine's journey of 160 years: Repurposal of an old urinary antiseptic for treatment and hypoxic radiosensitization of cancers and glioblastoma.

Methenamine (hexamethylenetetramine, hexamine, urotropine) is a compound discovered in 1859, which is still currently being used as a urinary antiseptic. Methenamine is highly soluble in water and polar solvents, and its molecular constitution is similar to adamantane compounds with tetrahedral cage like structure. In acidic conditions, methenamine decomposes to formaldehyde and ammonia. Recently, methenamine has gained a renewal of interest due to antibiotic-resistant bacteria urinary tract infections; interestingly, bacteria cannot gain resistance to formaldehyde. In 1968, David and Burkitt reported remarkable regression of four Burkitt Lymphoma patients in eight subjects who were treated with septicemine (a solution containing 6.3 g of methenamine iodomethylate and 1 g of methenamine sodium benzoate in 100 cc distilled water). Unfortunately, these striking observations did not gain interest in the medical community; despite experimental models that showed that methenamine synergized with hyperthermia, radiation, and chemotherapy to block cancer growth. As the hypoxic core of tumours have an acidic pH, it would be plausible to expect that methenamine would selectively target dormant, non-proliferative, and treatment-resistant cancer clones in large tumours. Moreover, previous data suggests that methenamine can be safely used intravenously and for treatment of infections of the central nervous system. It may therefore be an effective adjuvant in treatment of systemic cancers and glioblastoma.

Antibiotic use and infections in nursing homes. / Antibiotikabruk og infeksjoner i sykehjem.

BACKGROUND: Residents in nursing homes have a higher risk of developing infections that require antibiotic treatment than elderly people living at home. Use of antibiotics may cause adverse effects and result in the development of antimicrobial resistance. MATERIAL AND METHOD: Data on healthcare-associated infections and antibiotic use in 540 Norwegian nursing homes were retrieved from the Norwegian Institute of Public Health's point prevalence survey in the spring of 2016. Based on information on drug, dosage and indication, we assessed whether the use of antibiotics for the treatment of UTIs was in accordance with the National Guidelines for the Use of Antibiotics in Primary Care. RESULTS: UTI was the most commonly occurring type of infection, with a prevalence of 2.7 %. Prescription of first-line antibiotics accounted for approximately 60 % of the prescriptions for treatment of this illness. Choice of drug, dosage and microbiological testing when treating lower UTIs was not always in accordance with the national guidelines. The study showed widespread use of methenamine in Norwegian nursing homes. INTERPRETATION: The survey indicates that compliance with the national guidelines when treating lower UTIs could be improved with regard to the choice of drug, dosage and microbiological testing. Norwegian nursing home doctors should also consider whether their use of methenamine is in accordance with national and international recommendations.

Lower urinary tract infections in women.

In her lifetime, a woman is highly likely to develop at least one lower urinary tract infection. Early detection and treatment are key. Being aware of predisposing factors for infection and understanding appropriate diagnosis and treatment regimens will help nurses in both primary and acute care manage these patients correctly. This will not only benefit patients but will also help prevent incorrect antimicrobial management and avoid unplanned admissions. This aim of this article is to provide nurses with the information they need to best advise both colleagues and patients on how to manage lower urinary tract infections in women.

Australian Institute of Sport and the Australian Paralympic Committee position statement: urinary tract infection in spinal cord injured athletes.

Patients with spinal cord injuries are at increased risk of developing symptomatic urinary tract infections. Current evidence-based knowledge regarding prevention and treatment of urinary tract infection in the spinal cord injured population is limited. There are currently no urinary tract infection prevention and management guidelines specifically targeted towards elite spinal cord injured athletes. This position statement represents a set of recommendations intended to provide clinical guidelines for sport and exercise medicine physicians and other healthcare providers for the prevention and treatment of urinary tract infection in spinal cord injured athletes. It has been endorsed by the Australian Institute of Sport (AIS) and the Australian Paralympic Committee (APC).

UTIs in patients with neurogenic bladder.

Urinary tract infections (UTI) remain one of the most prevalent and frustrating morbidities for neurogenic bladder patients, and death attributed to urosepsis in the spinal cord injury (SCI) patient is higher when compared to the general population. Risk factors include urinary stasis, high bladder pressures, bladder stones, and catheter use. While classic symptoms of UTI include dysuria, increased frequency and urgency, neurogenic bladder patients present differently with increased spasticity, autonomic dysreflexia, urinary incontinence, and vague pains. Multiple modalities have been assessed for prevention including catheter type, oral supplements, bladder irrigation, detrusor injections and prophylactic antimicrobials. Of these, bladder inoculation with E. coli HU2117, irrigation with iAluRil(®), detrusor injections, and weekly prophylaxis with alternating antibiotics appear to have a positive reduction in UTI but require further study. Ultimately, treatment for symptomatic UTI should account for the varied flora and possible antibiotic resistances including relying on urine cultures to guide antibiotic therapy.

Methenamine for urinary tract infection prophylaxis: A systematic review.

Urinary tract infections (UTIs) commonly affect many patient populations. Recurrent UTIs (rUTIs) can be particularly problematic and lead to potential hospitalizations, multiple antibiotic courses, and have a potential negative impact on quality of life. To prevent UTIs, antibiotics are frequently used for prophylaxis; however, antibiotic prophylaxis has notable untoward consequences including but not limited to potential adverse effects and development of antibiotic resistance. Methenamine, an antiseptic agent initially available in 1967, has re-emerged as a potential option for UTI prophylaxis in various populations, including older adults and renal transplant recipients. The objective of this systematic review was to evaluate the clinical effectiveness and safety of methenamine for UTI prophylaxis. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance was performed. A PubMed, Embase, and Cochrane library search was conducted to identify relevant English-language studies evaluating methenamine for UTI prophylaxis including randomized controlled trials, case-control studies, and meta-analyses through June 2023. Articles were excluded if the studies did not primarily describe or evaluate methenamine for UTI prophylaxis, were commentaries/viewpoints articles, point prevalence studies, review articles, studies that evaluated methenamine used with another agent, and any duplicate publications from searched databases. A total of 11 articles were identified for inclusion. This systematic review suggests methenamine generally appears to be an effective and well-tolerated antibiotic-sparing option for UTI prophylaxis. Furthermore, the pharmacology, dosage and formulation, warnings, precautions, and safety considerations of methenamine that provide potential clinical considerations regarding its use for UTI prophylaxis are described. Further studies are needed to evaluate the clinical utility of methenamine for UTI prophylaxis.

Cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis for the management of recurrent urinary tract infections in secondary care: a multicentre, open-label, randomised, non-inferiority trial.

OBJECTIVES: To estimate the cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis in the management of recurrent urinary tract infections. DESIGN: Multicentre, open-label, randomised, non-inferiority trial. SETTING: Eight centres in the UK, recruiting from June 2016 to June 2018. PARTICIPANTS: Women aged ≥18 years with recurrent urinary tract infections, requiring prophylactic treatment. INTERVENTIONS: Women were randomised to receive once-daily antibiotic prophylaxis or twice-daily methenamine hippurate for 12 months. Treatment allocation was not masked and crossover between arms was allowed. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary economic outcome was the incremental cost per quality-adjusted life year (QALY) gained at 18 months. All costs were collected from a UK National Health Service perspective. QALYs were estimated based on responses to the EQ-5D-5L administered at baseline, 3, 6, 9, 12 and 18 months. Incremental costs and QALYs were estimated using an adjusted analysis which controlled for observed and unobserved characteristics. Stochastic sensitivity analysis was used to illustrate uncertainty on a cost-effectiveness plane and a cost-effectiveness acceptability curve. A sensitivity analysis, not specified in the protocol, considered the costs associated with antibiotic resistance. RESULTS: Data on 205 participants were included in the economic analysis. On average, methenamine hippurate was less costly (-£40; 95% CI: -684 to 603) and more effective (0.014 QALYs; 95% CI: -0.05 to 0.07) than antibiotic prophylaxis. Over the range of values considered for an additional QALY, the probability of methenamine hippurate being considered cost-effective ranged from 51% to 67%. CONCLUSIONS: On average, methenamine hippurate was less costly and more effective than antibiotic prophylaxis but these results are subject to uncertainty. Methenamine hippurate is more likely to be considered cost-effective when the benefits of reduced antibiotic use were included in the analysis. TRIAL REGISTRATION NUMBER: ISRCTN70219762.

Antimicrobial prescribing in nursing homes in Finland: results of three point prevalence surveys.

PURPOSE: The purpose of this study was to analyse the Finnish European Surveillance of Antimicrobial Consumption (ESAC) nursing home (NH) point prevalence surveys' (PPSs) data in detail, i.e. to evaluate the variability in the prevalence of antimicrobial prescription between NHs and its relationship to resident characteristics. METHODS: All residents present in NHs for ≥ 24 h and receiving systemic antimicrobials on the day of the survey were included. Data on antimicrobials and their indications (prophylaxis or treatment, type of infection) were collected. RESULTS: Three PPSs were performed: eight NHs participated in April and November 2009 and nine in May-September 2010. In total, there were 5,691 eligible residents (range by survey, 1,706-2,320; range by NH, 60-688), 716 (12.6 %; range by NH, 3.2-33.3 %) of which received at least one antimicrobial and 40 residents received two. The most common indication was prophylaxis (487/5,691, 8.6 %), mainly for urinary tract infection (UTI) (460/487, 94.5 %). Of the residents, 269/5,691 (4.7 %, range by NH, 1.5-6.0 %) were on antimicrobial treatment. UTI (119/269; 44.2 %) was the most common indication for treatment. Methenamine (306/756, 40.5 %) was the most commonly used antimicrobial, followed by trimethoprim (13.6 %) and pivmecillinam (11.0 %). In the eight NHs participating in all three surveys, the prevalence of residents receiving antimicrobials decreased from 16.6 to 9.7 %. CONCLUSIONS: Antimicrobial use was common in NHs in Finland and most were used for UTI prophylaxis and treatment. The usage, however, varied among NHs and tended to decrease during the surveys. NHs may benefit from antimicrobial stewardship interventions focused on UTI.

Use of antibiotics in nursing homes--surveillance with different methods.

BACKGROUND: Residents in nursing homes have a heightened risk of developing infections that should be treated with antibiotics. Inappropriate use of antibiotics may generate drug-related problems and increase resistance. In this study, we describe the use of antibiotics in nursing homes on the basis of prevalence surveys and drug sales statistics. MATERIAL AND METHODS: Five nursing homes in Oslo participated in two one-day surveys in 2009. All use of systemic antibiotics was registered. The data collection was undertaken according to a protocol developed by the European Surveillance of Antimicrobial Consumption (ESAC) Network and was part of a European study. The nursing homes' drug sales statistics for systemic antibiotics during 2009, distributed by the number of bed days for each nursing home, were estimated. Information on indications for each antibiotic from the prevalence surveys was collated with sales data to achieve an estimate of how the purchased antibiotics were used. RESULTS: The prevalence surveys showed that more than 8% of the residents received antibiotics. Prophylactic treatment accounted for 33% of the prescriptions. A prevalence of antibiotic use of 10% was estimated from the drug sales statistics. Urinary tract infection was the most frequently registered indication. Pivmecillinam and methenamine were most frequently prescribed and most frequently purchased. Most courses of treatment were prescribed in accordance with the national guidelines for antibiotic use. INTERPRETATION: The results from the drug sales statistics concurred well with the prevalence surveys, and the methods can thus be relevant for purposes of monitoring the use of antibiotics.

Methenamine hippurate for preventing urinary tract infections.

BACKGROUND: Methenamine salts are often used as an alternative to antibiotics for the prevention of urinary tract infection (UTI). This review was first published in Issue 1, 2002 and updated in Issue 4, 2007. OBJECTIVES: To assess the benefits and harms of methenamine hippurate in preventing UTI. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library), MEDLINE (from 1950), EMBASE (from 1980), reference lists of articles and abstracts from conference proceedings without language restriction. Manufacturers' of methenamine salts were contacted for unpublished studies and contact was made with known investigators.Date of last search: June 2012 SELECTION CRITERIA: Randomised controlled trials (RCT) and quasi-RCTs of methenamine hippurate used for the prevention of UTIs in all population groups were eligible. A comparison with a control/no treatment group was a prerequisite for selection. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as risk ratio (RR) for dichotomous outcomes with 95% confidence intervals (CI). An exploration of heterogeneity and a detailed description of results, grouped by population, was undertaken. MAIN RESULTS: Thirteen studies (2032 participants) were included. Six studies (654 patients) reported symptomatic UTI and eight studies (796 patients) reported bacteriuria. Overall, study quality was mixed. The overall pooled estimates for the major outcome measures were not interpretable because of underlying heterogeneity. Subgroup analyses suggested that methenamine hippurate may have some benefit in patients without renal tract abnormalities (symptomatic UTI: RR 0.24, 95% CI 0.07 to 0.89; bacteriuria: RR 0.56, 95% CI 0.37 to 0.83), but not in patients with known renal tract abnormalities (symptomatic UTI: RR 1.54, 95% CI 0.38 to 6.20; bacteriuria: RR 1.29, 95% CI 0.54 to 3.07). For short-term treatment duration (1 week or less) there was a significant reduction in symptomatic UTI in those without renal tract abnormalities (RR 0.14, 95% CI 0.05 to 0.38). The rate of adverse events was low. AUTHORS' CONCLUSIONS: Methenamine hippurate may be effective for preventing UTI in patients without renal tract abnormalities, particularly when used for short-term prophylaxis. It does not appear to work in patients with neuropathic bladder or in patients who have renal tract abnormalities. The rate of adverse events was low, but poorly described.There is a need for further large well-conducted RCTs to clarify this question, particularly for longer term use for people without neuropathic bladder.

Methenamine Hippurate With Cranberry Capsules Versus Cranberry Alone for Urinary Tract Infection Prevention in a Short-Term Indwelling Foley Catheter Population After Urogynecologic Surgery: A Double-Blinded Randomized Controlled Trial.

IMPORTANCE: There is little consensus on an effective nonantibiotic agent for the prevention of urinary tract infection (UTI) after pelvic reconstructive surgery. OBJECTIVE: The aim of the study was to investigate the impact of methenamine hippurate with cranberry capsules on rates of UTI after pelvic reconstructive surgery, among patients requiring short-term catheterization. STUDY DESIGN: In this randomized, double-blinded placebo-controlled trial, patients discharged with a catheter after pelvic reconstructive surgery were approached to participate. Participants were randomized to receive cranberry with methenamine or cranberry with placebo. Primary outcome was number of UTIs treated within 1 week after surgery. Secondary outcomes included incidence of UTIs treated within 6 weeks postoperatively, bacterial species on culture, urinary pH, catheter duration, patient adherence, and satisfaction. A sample size of 88 participants per arm was planned. RESULTS: From June 2019 to July 2021, 185 patients were randomized and 182 analyzed; 89 received placebo and 93 received methenamine. Both groups were similar. Incidence of UTI at 1 week was significantly higher in the placebo group (79.8%) compared with the methenamine group (66.7%; odds ratio, 1.97; 95% confidence interval, 1.01-3.87; P = 0.048). This difference increased by 6 weeks postoperatively (89.9% vs 72.0%; odds ratio, 3.45; 95% confidence interval, 1.51-7.87; P = 0.003). There were fewer pseudomonal UTIs in the methenamine group (P = 0.041). Duration of catheterization and urinary pH were similar. Overall adherence and level of satisfaction was high. CONCLUSIONS: In this high-risk population, methenamine was well tolerated and significantly reduced UTI rates. Methenamine with cranberry should be considered as an effective prophylactic therapy to reduce this common complication after pelvic surgery.