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Clinical Microbiology and Infection :... Jun 2017Nitrofurantoin has been used for the prevention of urinary tract infection (UTI) for over 60 years. We conducted a systematic review and meta-analysis to assess its... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Nitrofurantoin has been used for the prevention of urinary tract infection (UTI) for over 60 years. We conducted a systematic review and meta-analysis to assess its efficacy and safety in the prophylaxis of UTI.
METHODS
We performed a systematic review of all controlled trials in humans assessing nitrofurantoin for UTI prophylaxis published from 1946 to 2015. We further reviewed population-level cohort studies evaluating nitrofurantoin's toxicity. Meta-analyses assessing efficacy and adverse events were conducted on controlled trials.
RESULTS
Twenty-six controlled trials including 3052 patients fulfilled entry criteria for the systematic review and meta-analysis on efficacy and toxicity, and 16 population-level cohort studies were identified for review of toxicity. Overall quality was poor, with all studies at increased risk for various biases. When compared with no prophylaxis, nitrofurantoin is effective in the prevention of UTI (risk ratio 0.38 in favour of nitrofurantoin, 95% CI 0.30-0.48). Its prophylactic efficacy is superior to that of methenamine hippurate and comparable to that of other antibacterials. Compared with patients receiving other antibacterials, those receiving nitrofurantoin had an increased risk of 2.24 (95% CI 1.77-2.83) for a non-severe adverse effect. In all controlled trials, only one patient experienced a severe adverse effect (interstitial pneumonia). Cohort studies reported severe adverse effect frequencies of 0.02-1.5 per 1000 nitrofurantoin users.
CONCLUSIONS
Nitrofurantoin is effective in the prevention of UTI. Its use may be associated with increased non-severe adverse effects; severe adverse effects occur infrequently. The risk of severe toxicity seems to increase with the duration of nitrofurantoin prophylaxis.
Topics: Anti-Infective Agents, Urinary; Controlled Clinical Trials as Topic; Female; Humans; Nitrofurantoin; Treatment Outcome; Urinary Tract Infections
PubMed: 27542332
DOI: 10.1016/j.cmi.2016.08.003 -
The Cochrane Database of Systematic... Oct 2012Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). This is the third update of our review first... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). This is the third update of our review first published in 1998 and updated in 2004 and 2008.
OBJECTIVES
To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations.
SEARCH METHODS
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library) and the Internet. We contacted companies involved with the promotion and distribution of cranberry preparations and checked reference lists of review articles and relevant studies.Date of search: July 2012
SELECTION CRITERIA
All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products for the prevention of UTIs.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane risk of bias assessment tool.
MAIN RESULTS
This updated review includes a total of 24 studies (six cross-over studies, 11 parallel group studies with two arms; five with three arms, and two studies with a factorial design) with a total of 4473 participants. Ten studies were included in the 2008 update, and 14 studies have been added to this update. Thirteen studies (2380 participants) evaluated only cranberry juice/concentrate; nine studies (1032 participants) evaluated only cranberry tablets/capsules; one study compared cranberry juice and tablets; and one study compared cranberry capsules and tablets. The comparison/control arms were placebo, no treatment, water, methenamine hippurate, antibiotics, or lactobacillus. Eleven studies were not included in the meta-analyses because either the design was a cross-over study and data were not reported separately for the first phase, or there was a lack of relevant data. Data included in the meta-analyses showed that, compared with placebo, water or not treatment, cranberry products did not significantly reduce the occurrence of symptomatic UTI overall (RR 0.86, 95% CI 0.71 to 1.04) or for any the subgroups: women with recurrent UTIs (RR 0.74, 95% CI 0.42 to 1.31); older people (RR 0.75, 95% CI 0.39 to 1.44); pregnant women (RR 1.04, 95% CI 0.97 to 1.17); children with recurrent UTI (RR 0.48, 95% CI 0.19 to 1.22); cancer patients (RR 1.15 95% CI 0.75 to 1.77); or people with neuropathic bladder or spinal injury (RR 0.95, 95% CI: 0.75 to 1.20). Overall heterogeneity was moderate (I² = 55%). The effectiveness of cranberry was not significantly different to antibiotics for women (RR 1.31, 95% CI 0.85, 2.02) and children (RR 0.69 95% CI 0.32 to 1.51). There was no significant difference between gastrointestinal adverse effects from cranberry product compared to those of placebo/no treatment (RR 0.83, 95% CI 0.31 to 2.27). Many studies reported low compliance and high withdrawal/dropout problems which they attributed to palatability/acceptability of the products, primarily the cranberry juice. Most studies of other cranberry products (tablets and capsules) did not report how much of the 'active' ingredient the product contained, and therefore the products may not have had enough potency to be effective.
AUTHORS' CONCLUSIONS
Prior to the current update it appeared there was some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. The addition of 14 further studies suggests that cranberry juice is less effective than previously indicated. Although some of small studies demonstrated a small benefit for women with recurrent UTIs, there were no statistically significant differences when the results of a much larger study were included. Cranberry products were not significantly different to antibiotics for preventing UTIs in three small studies. Given the large number of dropouts/withdrawals from studies (mainly attributed to the acceptability of consuming cranberry products particularly juice, over long periods), and the evidence that the benefit for preventing UTI is small, cranberry juice cannot currently be recommended for the prevention of UTIs. Other preparations (such as powders) need to be quantified using standardised methods to ensure the potency, and contain enough of the 'active' ingredient, before being evaluated in clinical studies or recommended for use.
Topics: Beverages; Capsules; Cross-Over Studies; Female; Humans; Male; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic; Recurrence; Sex Factors; Tablets; Urinary Tract Infections; Vaccinium macrocarpon
PubMed: 23076891
DOI: 10.1002/14651858.CD001321.pub5 -
Pharmacotherapy Feb 2024Urinary tract infections (UTIs) commonly affect many patient populations. Recurrent UTIs (rUTIs) can be particularly problematic and lead to potential hospitalizations,... (Review)
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.
Topics: Humans; Aged; Methenamine; Quality of Life; Urinary Tract Infections; Anti-Bacterial Agents; Treatment Outcome; Antibiotic Prophylaxis
PubMed: 37986168
DOI: 10.1002/phar.2895 -
International Urogynecology Journal Mar 2024Antibiotic resistance is an unavoidable consequence of antibiotic use and growing rates of resistance are an urgent issue. Methenamine is a non-antibiotic alternative... (Review)
Review
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.
Topics: Humans; Methenamine; Prospective Studies; Retrospective Studies; Urinary Tract Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis
PubMed: 38329493
DOI: 10.1007/s00192-024-05726-2 -
Current Opinion in Urology Nov 2023Recurrent urinary tract infections (rUTIs) in women are prevalent and difficult to manage. The rise of antimicrobial resistance makes it prudent to re-investigate the...
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.
Topics: Adult; Female; Humans; Methenamine; Urinary Tract Infections; Hippurates; Anti-Bacterial Agents
PubMed: 37337660
DOI: 10.1097/MOU.0000000000001108 -
The British Journal of General Practice... Jul 2021Urinary tract infections (UTIs) are often treated with antibiotics and are a source of antibiotic overuse. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Urinary tract infections (UTIs) are often treated with antibiotics and are a source of antibiotic overuse.
AIM
To systematically review randomised controlled trials (RCTs) of adult women in the community with a history of recurrent UTIs and who use methenamine hippurate prophylactically.
DESIGN AND SETTING
Systematic review of women in the UK, Australia, Norway, and US (aged ≥18 years) with recurrent UTIs receiving methenamine hippurate against placebo or no treatment, and antibiotics.
METHOD
The authors searched three databases, clinical trial registries, and performed forward-backward citation analysis on references of included studies.
RESULTS
Six studies involving 557 participants were included (447 were analysed). Of the six studies, five were published and one was an unpublished trial record with results, three compared methenamine hippurate against placebo or control, and three compared methenamine hippurate with antibiotics. For the number of patients who remained asymptomatic, methenamine hippurate showed a non-statistically significant trend of benefit versus antibiotics over 12 months (risk ratio [RR] 0.65, 95% confidence interval [CI] = 0.40 to 1.07, 49%), versus control over 6 or 12 months (RR 0.56, 95% CI = 0.13 to 2.35, 93%), and a non-statistically significant trend versus any antibiotic for abacteruria (RR 0.80, 95% CI = 0.62 to 1.03, 23%). A similar non-statistically significant trend of benefits for methenamine hippurate for the number of UTI or bacteriuric episodes was found, and a non-statistically significant difference in the number of patients experiencing adverse events between methenamine hippurate and any comparator, with a trend towards benefit for the methenamine hippurate, was identified. Antibiotic use and resistance were not consistently reported.
CONCLUSION
There is insufficient evidence to be certain of the benefits of methenamine hippurate to prevent UTI. Further research is needed to test the drug's effectiveness in preventing UTIs and as an alternative for antibiotic treatment for UTI.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Female; Hippurates; Humans; Methenamine; Pharmaceutical Preparations; Urinary Tract Infections
PubMed: 34001538
DOI: 10.3399/BJGP.2020.0833 -
Translational Andrology and Urology May 2018Urinary tract infection (UTI) is a source of morbidity and healthcare costs in adults with spina bifida (ASB). UTI prevention strategies are often recommended, but the... (Review)
Review
Urinary tract infection (UTI) is a source of morbidity and healthcare costs in adults with spina bifida (ASB). UTI prevention strategies are often recommended, but the evidence of various approaches remains unclear. We performed a systematic review to inform a best practice policy statement for UTI prevention in ASB. On behalf of the Neurogenic Bladder Research Group (NBRG.org), we developed an a priori protocol and searched the published English literature for 30 outcomes questions addressing UTI prevention in ASB. The questions spanned the categories of antibiotics, oral supplements, bladder management factors and social support. Where there was little literature in ASB, we included literature from similar populations with neurogenic bladder (NB). Data was abstracted and then reviewed with recommendations made by consensus of all authors. Level of Evidence (LoE) and Grade of Recommendation (GoR) were according to the Oxford grading system. Of 6,433 articles identified by our search, we included 99 publications. There was sufficient evidence to support use of the following: saline bladder irrigation (LoE 1, GoR B), gentamicin bladder instillation (LoE 3, GoR C), single-use intermittent catheterization (IC) (LoE 2, GoR B), hydrophilic catheters for IC (LoE 2, GoR C), intradetrusor onabotulinumtoxinA injection (LoE 3, GoR C), hyaluronic acid (HA) instillation (LoE 1, GoR B), and care coordination (LoE 3, GoR C). There was sufficient evidence to recommend against use of the following: sterile IC (LoE 1, GoR B), oral antibiotic prophylaxis (LoE 2, GoR B), treatment of asymptomatic bacteriuria (LoE 2, GoR B), cranberry (LoE 2, GoR B), methenamine salts (LoE 1, GoR B), and ascorbic acid (LoE1, GoR B). There was insufficient evidence to make a recommendation for other outcomes. Overall, there are few studies in UTI prevention in the specific population of ASB. Research in populations similar to ASB helps to guide recommendations for UTI prevention in the challenging patient group of ASB. Future studies in UTI prevention specific to ASB are needed and should focus on areas shown to be of benefit in similar populations.
PubMed: 29928619
DOI: 10.21037/tau.2018.04.21 -
BMJ Clinical Evidence Jul 2008Cystitis is a bacterial infection of the lower urinary tract which causes pain when passing urine, and causes urgency, haematuria, and suprapubic pain not associated... (Review)
Review
INTRODUCTION
Cystitis is a bacterial infection of the lower urinary tract which causes pain when passing urine, and causes urgency, haematuria, and suprapubic pain not associated with passing urine. Recurrent cystitis is usually defined as three episodes of urinary tract infection in the previous 12 months, or two episodes in the previous 6 months.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: Which interventions prevent further recurrence of cystitis in women experiencing at least two infections per year? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: continuous antibiotic prophylaxis (trimethoprim, co-trimoxazole, nitrofurantoin, cefaclor, or a quinolone or cephalexin); continuous prophylaxis with methenamine hippurate; cranberry juice and cranberry products; oestrogen (topical) in postmenopausal women; passing urine after intercourse; postcoital antibiotic prophylaxis; single-dose self-administered antibiotic.
Topics: Acute Disease; Bacterial Infections; Cystitis; Female; Humans; Incidence; Nitrofurantoin; Prospective Studies; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections
PubMed: 19445741
DOI: No ID Found -
The Spine Journal : Official Journal of... Jun 2023Complications such as pressure sores, pulmonary infection, urinary tract infection (UTI), and venous thromboembolism (VTE) are common after spinal cord injury (SCI).... (Review)
Review
BACKGROUND CONTEXT
Complications such as pressure sores, pulmonary infection, urinary tract infection (UTI), and venous thromboembolism (VTE) are common after spinal cord injury (SCI). These have serious consequences for patients' physical, social, and vocational well-being. Several authoritative organizations have developed guidelines for managing these complications after SCI.
PURPOSE
We aim to systematically review and appraise guidelines on the management of four common complications (pressure sores, pulmonary infection, UTI, and VTE) after SCI as well as to summarize relevant recommendations and assess the quality of their supporting evidence.
DESIGN
Systematic review.
METHODS
We searched Medline, Embase, Cochrane, and Web of Science, as well as guideline-specific databases (eg, National Guideline Clearinghouse) and Google Scholar, from January 2000 to January 2022. We included the most updated guidelines developed by specific authoritative organizations. We evaluated the included guidelines using the Appraisal of Guidelines for Research and Evaluation 2nd edition instrument, which measures six domains (eg, applicability). Recommendations extracted from guidelines were categorized as for, against, or neither for nor against. An evidence assessment was adopted to classify the quality of supporting evidence as poor, fair, or good.
RESULTS
Eleven guidelines from 2005 to 2020 were included, all of which, among the six domains, scored lowest in the domain of applicability. For pressure sores, guidelines recommended for skin inspection, repositioning, and the use of pressure reduction equipment as preventive measures and dressings, debridement, and surgery as treatment measures. For pulmonary infection, guidelines recommended for physical (eg, the use of an insufflation-exsufflation device) and pharmacological measures (eg, the use of bronchodilators). For UTI, guidelines recommended for antibiotics as a treatment measure but recommended against cranberries, methenamine salts, and acidification or alkalinization agents as preventive measures. For VTE prophylaxis, five guidelines recommended for low molecular weight heparin (LMWH). Three guidelines recommended against unfractionated heparin, whereas one guideline recommended for it. Most of the supporting evidence was of poor quality (130/139), and the rest was of fair quality (9/139).
CONCLUSIONS
For pressure sores, pulmonary infection, and UTI, evidence of poor to fair quality indicated consistent recommendations for prevention and treatment measures. For VTE, LMWH was consistently recommended, whereas recommendations on the use of unfractionated heparin were controversial.
Topics: Humans; Heparin; Heparin, Low-Molecular-Weight; Venous Thromboembolism; Pressure Ulcer; Spinal Cord Injuries; Anticoagulants
PubMed: 36521679
DOI: 10.1016/j.spinee.2022.12.001 -
The Cochrane Database of Systematic... Oct 2012Methenamine 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... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Anti-Infective Agents, Urinary; Hippurates; Humans; Methenamine; Randomized Controlled Trials as Topic; Urinary Tract Infections
PubMed: 23076896
DOI: 10.1002/14651858.CD003265.pub3