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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., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

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., Competing Interests: Competing interests: CH reports personal fees from Astellas Pharma (Tokyo, Japan), Medtronic plc (Dublin, Ireland), Allergan Ltd (Dublin, Ireland), GlaxoSmithKline plc (Brentford, UK), Teleflex Medical Inc (Temecula, California, USA), Viatris (Canonsburg, Pennsylvania, USA) and grants from Medtronic plc, the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (HTA 15/40/05) and The Urology Foundation (London, UK) outside the submitted work. LV reports being the co-ordinating editor of Cochrane Incontinence (from 2016) and being a member of NIHR HTA, Clinical Evaluation and Trials Panel from 2015 to 2018. TC reports grants from the NIHR HTA programme (HTA 16/154/01, HTA 15/130/94 and HTA 11/72/01) during the conduct of the study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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., (© 2023 Pharmacotherapy Publications, Inc.)

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., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pneumocystis jirovecii pneumonia (PJP) remains an important cause of morbidity and mortality in non-HIV immunocompromised patients especially in transplant recipients. But its diagnosis remains challenging due to the insuffificient performance of conventional methods for diagnosing Pneumocystis jirovecii(P. jirovecii) infection. Therefore, the auxiliary diagnostic function of metagenomics next-generation sequencing (mNGS) in clinical practice is worth of exploring., Method: 34 non-HIV immunocompromised patients who were diagnosed as PJP by clinical manifestations, imaging findings, immune status of the host, and Methenamine silver staining were tested by mNGS from October 2018 to December 2020 in Sichuan Provincial People's Hospital. The clinical performances of mNGS for P. jirovecii infection diagnosis were also evaluated with genome reads abundance and comparing with other traditional diagnostic methods., Results: We diagnosed a total of 34 non-HIV PJP patients by the clinical composite diagnosis. Our data shows that, compared with the clinical microbiological test, the detection rate of mNGS for P. jirovecii in non-HIV infected PJP patients is significantly higher than that of Methenamine silver staining and serum 1-3-β-D-glucan. mNGS can be used as an auxiliary diagnostic tool to help diagnosis. The number of reads mapped to the genome of P. jirovecii and the duration of patients from onset to sampling collection were statistically significant between the two groups (Reads>100 and Reads ≤ 100) (8days vs . 23days, p =0.020). In addition, univariate analysis showed that C-reactive protein (15.8mg/L vs .79.56mg/L, p =0.016), lactate dehydrogenase (696U/l vs . 494U/l, p =0.030) and procalcitonin (0.09ng/ml vs . 0.59ng/ml, p =0.028) was also statistically significant between the two groups., Conclusions: An effective detection rate was achieved in PJP patients using mNGS testing of bronchoalveolar lavage fluid (BALF) or blood. The study also confirmed that the abundance of reads of P. jirovecii is related to the interval between the onset and sample collection. And the inflammation status during simultaneous mNGS detection might determine the abundance of pathogens. Hence, we conclude that the mNGS strategy could benefit disease diagnosis as well as treatment when complicated clinical infections appeared., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Yue, Wu, Gao, He and Pan.)

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.

Importance: Antibiotics are commonly used to treat and prevent urinary tract infection (UTI), but resistance is growing. Nonantibiotic prophylaxis such as methenamine hippurate (MH) shows clinical promise, but its impact on bladder factors influencing recurrent UTIs (rUTIs) is not well described., Objective: The aim of the study was to examine the effect of MH on bladder inflammation and barrier function in aged mice and women with rUTI., Study Design: This study included urine samples from an experimental study involving aged female mice with and without methenamine treatment as well as women with rUTI who received either no prophylaxis, MH alone, vaginal estrogen therapy and/or d-mannose alone, or MH in addition to vaginal estrogen therapy and/or d-mannose. We performed a comprehensive cytopathological analysis, which included enzyme-linked immunosorbent assay for immunoglobulin A (IgA), interleukin 6 (in human samples), and fluorescein isothiocyanate-conjugated-dextran permeability assay (in mice) to assess for urothelial permeability., Results: In the aged mice model, there was a decreased urothelial permeability (as seen by retention of fluorescein isothiocyanate-conjugated-dextran fluorescence in superficial cells) and increased urinary IgA in mice treated with MH compared with controls. There was no significant difference in urothelial shedding (P > 0.05). In human samples, there was significantly increased urinary IgA in those taking MH alone compared with no prophylaxis (830.1 vs 540.1 ng/mL, P = 0.04), but no significant difference in interleukin 6., Conclusions: Methenamine hippurate seems to enhance barrier function as evidenced by decreased urothelial permeability and increased urinary IgA levels, without worsening inflammation. This may reflect another beneficial mechanism by which MH helps prevent rUTI., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2022 American Urogynecologic Society. All rights reserved.)

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., (© 2021. The International Urogynecological Association.)

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., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2022 American Urogynecologic Society. All rights reserved.)

Introduction: Recurrent urinary tract infections remain a challenge in solid organ transplant and have a negative impact on morbidity/mortality., Project Aim: The purpose of this program evaluation was to determine the impact of methenamine on recurrent urinary tract infection in kidney and liver-kidney transplant recipients., Design: This retrospective review included patients > 18 years of age who received a kidney or liver-kidney transplant. Patients were divided into the following groups: (1) Methenamine therapy initiation received methenamine for ≥ 180 days or (2) Non-methenamine therapy: did not receive recurrent urinary tract infection prophylaxis. A total of 60 patients were included., Results: When comparing outcomes between methenamine therapy initiation and non-methenamine therapy group, a significant reduction in the rate of recurrent urinary tract infection was reported in the methenamine therapy initiation group (0.6 vs 1.3 per 180 patient days follow-up, P = 0.0005). A significant reduction was also noted with rate of asymptomatic bacteriuria, treatment failures, bacteremia, hospitalizations due to recurrent urinary tract infection, multi-drug resistant organism isolated, and the average duration of antibiotic use. A significant difference in the time to failure of methenamine therapy initiation versus non-methenamine therapy is noted up to 180 patient-days follow-up (RR 1.56, P = 0.0019)., Conclusion: This evaluation supported methenamine therapy for recurrent urinary tract infection in kidney and liver-kidney transplant. The most significant impact of methenamine recurrent urinary tract infection was seen in the first 30 days after initiation.

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, I 2 49%), versus control over 6 or 12 months (RR 0.56, 95% CI = 0.13 to 2.35, I 2 93%), and a non-statistically significant trend versus any antibiotic for abacteruria (RR 0.80, 95% CI = 0.62 to 1.03, I 2 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., (© The Authors.)

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.

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., (© 2019 John Wiley & Sons Australia, Ltd.)

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.

Urinary tract infections (UTIs) are highly prevalent, lead to considerable patient morbidity, incur large financial costs to health-care systems and are one of the most common reasons for antibiotic use worldwide. The growing problem of antimicrobial resistance means that the search for nonantibiotic alternatives for the treatment and prevention of UTI is of critical importance. Potential nonantibiotic measures and treatments for UTIs include behavioural changes, dietary supplementation (such as Chinese herbal medicines and cranberry products), NSAIDs, probiotics, D-mannose, methenamine hippurate, estrogens, intravesical glycosaminoglycans, immunostimulants, vaccines and inoculation with less-pathogenic bacteria. Some of the results of trials of these approaches are promising; however, high-level evidence is required before firm recommendations for their use can be made. A combination of these agents might provide the optimal treatment to reduce recurrent UTI, and trials in specific population groups are required.

Background: At least half of all adult women will experience infective cystitis (urinary tract infection: UTI) at least once in their life and many suffer from repeated episodes. Recurrent urinary tract infection (rUTI) in adult women is usually treated with long-term, low-dose antibiotics and current national and international guidelines recommend this as the 'gold standard' preventative treatment. Although they are reasonably effective, long-term antibiotics can result in bacteria becoming resistant not only to the prescribed antibiotic but to other antimicrobial agents. The problem of antimicrobial resistance is recognised as a global threat and the recent drive for antibiotic stewardship has emphasised the need for careful consideration prior to prescribing antibiotics. This has led clinicians and patients alike to explore potential non-antibiotic options for recurrent UTI prevention., Design /methods: This is a multicentre, pragmatic, patient-randomised, non-inferiority trial comparing a non-antibiotic preventative treatment for rUTI in women, methenamine hippurate, against the current standard of daily low-dose antibiotics. Women who require preventative treatment for rUTI are the target population. This group is comprised of those with a diagnosis of rUTI, defined as three episodes in 1 year or two episodes in 6 months, and those with a single severe infection requiring hospitalisation. Participants will be recruited from secondary care urology / urogynaecology departments in the UK following referral with rUTI. Participants will be followed up during a 12-month period of treatment and in the subsequent 6 months following completion of the prophylactic medication. Outcomes will be assessed from patient recorded symptoms, quality of life questionnaires and microbiological examination of urine and perineal swabs. The primary outcome is the incidence of symptomatic antibiotic-treated UTI self-reported by participants during the 12-month period of preventative treatment. Health economic outcomes will also be assessed to define the cost-effectiveness of both treatments. A qualitative study will be conducted in the first 8 months of the trial to explore with participants/non-participants' and recruiting clinicians' views on trial processes and identify potential barriers to recruitment, reasons for participating and non-participation and for dropping out of the study., Discussion: The study was commissioned and funded by the National Institute for Health Research (NIHR) and approved under the Medicines and Healthcare products Regulatory Agency (MHRA) notification scheme as a 'Type A' study., Trial Registration: International Standard Randomised Controlled Trial Number (ISRCTN), registry number: ISRCTN70219762 . Registered on 31 May 2016.

Competing Interests: Conflicts of Interest: CH reports speaker fees from Astellas, Pfizer, Ferring, Allergan, Medtronic, and is a member of the advisory boards for American Medical Systems and Pierre Fabre Pharmaceuticals. JB and RV have no conflicts to report.

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.

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.

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)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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.

In the era of multidrug resistance, it is critical to utilize antibiotics in an appropriate manner and to identify new treatments or revisit the use of 'forgotten' drugs. Because urinary tract infections (UTIs) are common, particularly in an increasing elderly population, the 'forgotten' drug, methenamine, may become important as a preventive therapy for recurrent UTIs. Methenamine, a urinary antibacterial agent, can be used as methenamine hippurate or methenamine mandelate preparations and is United States Food and Drug Administration-approved. This article discusses the place of preventive therapy for recurrent UTIs, chemistry, mechanism of action, pharmacology, clinical uses, dosage, adverse reactions and safety, and drug interactions of methenamine. Because of its unique antiseptic property, the authors suggest that methenamine should be considered when more commonly used antibiotics fail to suppress recurrent UTIs.

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.

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.

Background: The treatment of brain abscesses remains one of the success stories of contemporary neurosurgery; what began as a nearly uniformly fatal disease at the turn of the 20th century has become a largely curable ailment through the use of operative and pharmaceutical intervention., Methods: Following institutional review board approval, and through the courtesy of the Alan Mason Chesney Archives, the surgical files of the Johns Hopkins Hospital, 1896 to 1912, were reviewed., Results: A total of six patients were operated on for intracranial abscesses. Three patients died during their admission, the remaining three were discharged with a condition listed as "improved" or "well.", Conclusions: Cushing employed a variety of operative drainage techniques for intracranial abscesses and implemented an early antibacterial agent to provide adjuvant treatment in one patient. Although these cases demonstrate a 50% mortality rate, they provide insight into the challenges faced by neurosurgeons treating intracranial abscesses at the turn of the 20th century., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

Acute cystitis is one of the most common health-related problems in the female population. Over the last few decades, a number of drugs labeled as 'urinary tract analgesics' were released; these are available over the counter and are gaining widespread resonance among the North American population. The main representatives of this class of drugs are phenazopyridine and methenamine hippurate. Methenamine's efficacy and side effects have been well studied in a recent systematic review. On the other hand, in contrast to its widespread use, the published clinical evidence regarding phenazopyridine's effectiveness and safety is scarce. In addition, consumers (potentially patients) appear to ignore the limitations of this kind of treatment. In this article, concerns regarding the use of over-the-counter uroanalgesics, with a focus on the relevant clinical evidence, are discussed.

Background: Urinary tract infections (UTIs, including upper and lower symptomatic) are the most common infections in nursing homes and prevention may reduce patient suffering, antibiotic use and resistance. The spectre of agents used in preventing UTIs in nursing homes is scarcely documented and the aim of this study was to explore which agents are prescribed for this purpose., Methods: We conducted a one-day, point-prevalence study in 44 Norwegian nursing homes during April-May 2006. Nursing home residents prescribed any agent for UTI prophylaxis were included. Information recorded was type of agent and dose, patient age and gender, together with nursing home characteristics. Appropriateness of prophylactic prescribing was evaluated with references to evidence in the literature and current national guidelines., Results: The study included 1473 residents. 18% (n = 269) of the residents had at least one agent recorded as prophylaxis of UTI, varying between 0-50% among the nursing homes. Methenamine was used by 48% of residents prescribed prophylaxis, vitamin C by 32%, and cranberry products by 10%. Estrogens were used by 30% but only one third was for vaginal administration. Trimethoprim and nitrofurantoin were used as prophylaxis by 5% and 4%, respectively., Conclusions: The agents frequently prescribed to prevent UTIs in Norwegian nursing homes lack documented efficacy including methenamine and vitamin C. Recommended agents like trimethoprim, nitrofurantoin and vaginal estrogens are infrequently used. We conclude that prescribing of prophylactic agents for UTIs in nursing homes is not evidence-based.

Accurate diagnosis of root canal morphology and anatomy is essential for thorough shaping and cleaning of the entire root canal system and consequent successful root canal treatment. Mandibular premolars show a wide variety of root canal anatomy. This paper describes a case of mandibular second premolar with three root canals that has previously received an incomplete root canal treatment.

Background: Methenamine salts are often used as an alternative to antibiotics for the prevention of urinary tract infection (UTI)., Objectives: To assess the benefits and harms of methenamine hippurate in preventing UTI., Search Strategy: 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: September 2006, 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 relative risk (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.

Objective: To determine whether Methenamine Hippurate (MH) or cranberry tablets prevent urinary tract infections (UTI) in people with neuropathic bladder following spinal cord injury (SCI)., Study Design: Double-blind factorial-design randomized controlled trial (RCT) with 2 year recruitment period from November 2000 and 6 month follow-up., Setting: In total, 543 eligible predominantly community dwelling patients were invited to participate in the study, of whom 305 (56%) agreed., Methods: Eligible participants were people with SCI with neurogenic bladder and stable bladder management. All regimens were indistinguishable in appearance and taste. The dose of MH used was 1 g twice-daily. The dose of cranberry used was 800 mg twice-daily. The main outcome measure was the time to occurrence of a symptomatic UTI., Results: Multivariate analysis revealed that patients randomized to MH did not have a significantly longer UTI-free period compared to placebo (HR 0.96, 95% CI: 0.68-1.35, P=0.75). Patients randomized to cranberry likewise did not have significantly longer UTI-free period compared to placebo (HR 0.93, 95% CI: 0.67-1.31, P=0.70)., Conclusion: There is no benefit in the prevention of UTI from the addition of MH or cranberry tablets to the usual regimen of patients with neuropathic bladder following SCI.

A cross-sectional descriptive study among Norwegian nursing homes was conducted in 2003 to examine pharmacoepidemiological characteristics of antibacterials in nursing homes and also to estimate their share of overall antibacterial use in Norway. Antibacterial data were collected for ATC group J01 antibacterials for systemic use, A07AA09 vancomycin and P01AB01 metronidazole in DDDs/y. The amount of drugs principally prescribed for urinary tract infections (UTI) were depicted and used as an indicator for the treatment frequency for UTI in the nursing homes. Prescription of antibacterials in the 133 nursing homes that delivered data varied - from 4 to 44 DDD/100 bed-d. The urinary prophylactic agent, methenamine, represented nearly half of DDDs used, mean 7.3 DDD/100 bed-d. Penicillins with extended spectrum (J01CA) were most frequently used, followed by trimethoprim and sulfonamides (J01E), mean 2.3 and 1.5 DDD/100 bed-d, respectively. On average, 49% of the therapeutic antibacterials were drugs used for UTI, range 12%-88%. In 2003, the nursing home setting purchased an estimated 6% of human antibacterial use in Norway. Nursing homes represent an important share of national human use of antibacterials. The large variation in antibacterial use between facilities underlines the need for increased focus on rational prescribing in nursing homes.

Background: The use of bladder drainage to avoid urinary retention after gynecological surgery is more or less custom based, and duration of drainage varies considerably. In this paper the use of 1-day drainage by transurethral Foley catheter was investigated with regard to impaired voiding, asymptomatic bacteriuria, and urinary tract infection. Furthermore, the use of methenamine hippurate was studied with regard to postoperative asymptomatic bacteriuria and urinary tract infection. METHODS. This summary is based on six published papers totaling 917 patients. In three case series, 1-day catheterization was used in women undergoing gynecological laparotomy, colposuspension, or vaginal plastic surgery. To compare 1- and 3-day Foley catheterization, two open, randomized trials were performed on women undergoing vaginal plastic surgery or colposuspension. The last study was a double-blind trial between methenamine hippurate and placebo as prophylaxis against urinary tract infection and asymptomatic bacteriuria using 1-day catheterization., Results: Postoperative voiding problems and urinary tract infection occurred infrequently with 1-day catheterization, and no more frequently than with catheterization for three days. Methenamine hippurate decreased the incidence of urinary tract infection and asymptomatic bacteriuria by 80 and 40%, respectively., Conclusions: One-day bladder drainage by transurethral Foley catheter may be used routinely in common gynecological surgery with a low rate of voiding problems, asymptomatic bacteriuria, and urinary tract infection. Methenamine hippurate prophylaxis effectively reduces postoperative urinary tract infection.

Background: There is a high risk of postoperative bacteriuria and urinary tract infection after gynecologic surgery. Postoperative asymptomatic bacteriuria often disappears without treatment, but 15-20% of patients still require treatment for postoperative urinary tract infection. This study was carried out to assess the value of prophylactic treatment with methenamine hippurate after routine gynecologic surgery., Methods: This was a prospective, randomized, double-blind, placebo-controlled clinical trial comprising 145 patients undergoing routine gynecologic laparotomy or vaginal plastic surgery using a Foley catheter for 24 h. Antibiotics were not used. Subjects received 1 g Hiprex or placebo twice daily for 5 days. Urine was cultured preoperatively, at catheter removal, and 2 days later. Patients with positive cultures were not given antibiotics unless they were symptomatic. The follow-up period was 1 month., Statistics: The chi-square test, Fisher exact test, and t-test were used with level of significance at 0.05, and odds ratios with 95% confidence intervals were calculated., Results: Asymptomatic bacteriuria was diagnosed in 36 cases (50.0%) in the placebo group and 22 cases (30.1%) in the methenamine group (p = 0.02). Urinary tract infection was diagnosed in 10 cases (13.9%) in the placebo group and two cases (2.7%) in the methenamine group (p = 0.03). There were few adverse events., Conclusions: Prophylactic treatment with methenamine hippurate significantly reduces the incidence of postoperative bacteriuria and urinary tract infection.

Aim: The aim of this study was to evaluate the fate of microorganisms in root canals of teeth with infected pulps and periapical bone lesions with and without the use of calcium hydroxide medication., Methodology: Endodontic samples were cultured and microorganisms were counted and identified in 43 teeth before (sample 1) and after (sample 2) treatment during the first visit and before (sample 3) and after (sample 4) treatment during the second visit. In the first visit teeth were instrumented and half of the teeth were filled with a thick slurry of calcium hydroxide in sterile saline. The other teeth were obturated with gutta-percha and AH-2 6 sealer. After 4 weeks the teeth with calcium-hydroxide were accessed again and after microbiological sampling they were obturated with gutta-percha and AH-26 sealer., Results: The mean total colony forming unit (CFU) counts of positive samples dropped significantly as a result of canal preparation during the first visit from 1.0 x 10(6) to 1.8 x 10(3) (between samples 1 and 2) but increased to 9.3 x 10(3) in the period between the two visits (sample 2 and 3). There was no difference in mean total CFU counts of positive samples between the end of the first (sample 2) and the end of the second visit (sample 4). The most frequently isolated species were Prevotella intermedia, Capnocytophaga spp.. Actinomyces odontolyticus. Propionibacterium acnes and Peptostreptococcus micros., Conclusions: Although a calcium hydroxide paste was placed in the prepared canals, the number of positive canals had increased in the period between visits. However, the number of microorganisms had only increased to 0.93% of the original number of CFU (sample 1). It is concluded that a calcium hydroxide and sterile saline slurry limits but does not totally prevent regrowth of endodontic bacteria.

Background: Methenamine salts are often used for the prevention of urinary tract infection (UTI)., Objectives: To assess the effectiveness of methenamine hippurate in preventing UTI., Search Strategy: Published and unpublished randomised controlled trials were identified from the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, Current Contents, reference lists of review articles and retrieved trials. The manufacturers' of methenamine salts were contacted for unpublished studies and contact was made with known investigators in the area., Selection Criteria: Randomised and quasi-randomised trials of methenamine hippurate used for the prevention of UTIs in all population groups were eligible for inclusion. A comparison with a control (no treatment) group was a prerequisite to selection., Data Collection and Analysis: Two reviewers (BL and TB) performed independent assessment and data extraction using a standardised format. Discrepancies, methodological and interpretative issues were discussed with JS or JC. An exploration of heterogeneity as well as a detailed description of results grouped by population was conducted., Main Results: Eleven studies met the inclusion criteria. All trials were included in a descriptive analysis. Seven trials were included in meta-analyses. Four trials (199 patients) studied symptomatic bacteriuria and six trials (341 patients) studied bacteriuria as an outcome measure. Overall, trial quality was poor. The direction of six of the pooled trials was towards a favourable treatment effect from methenamine hippurate. Interpretation of the pooled estimates was not done in view of underlying heterogeneity. The study by Pettersson 1989 explained some, but not all, of the underlying heterogeneity. This study differed from all others by including patients with known upper renal tract abnormalities. Adverse reactions were mentioned by 10 studies. The rate of adverse events was low., Reviewer's Conclusions: There is not enough evidence to conclusively support the use of methenamine hippurate for urinary prophylaxis. An exploration of heterogeneity raises the (hypothesis generating) possibility that methenamine hippurate may have some efficacy in patients without but not in patients with known upper renal tract abnormality (with asymptomatic bacteriuria as the outcome measure). Due to the small sample size and methodological problems within the studies involved, interpretation of these data should be done cautiously. The rate of adverse events reported by the trials was low, which suggests that current usage is unlikely to be causing significant harm.

Aim: The aim of this study was to observe the existence and assess the quality of obturation of uninstrumented recesses in oval canals., Methodology: The balanced force technique was used in two groups of oval canals in human mandibular incisors. The canals in group 1 were enlarged to conventional sizes, whereas canals in group 2 were enlarged more widely. All canals were obturated with cold laterally condensed gutta-percha. Two horizontal sections were cut in the apical portion of each filled root. Images of the cross-sections were scanned and analysed using the KS100 Imaging system., Results: Uninstrumented recesses appeared in 13 (65%) oval canals. The recesses in five of these 13 canals were obturated without visible voids. The recesses in the other eight canals were either obturated with visible voids or completely unfilled. The percentage of filled area was significantly higher in group 1 than in group 2 (P < 0.05)., Conclusions: Uninstrumented recesses may be left in many oval canals after preparation using the balanced force technique and these recesses may often not be completely obturated with cold laterally condensed gutta-percha.

The aim of this study was to examine whether intracanal medication prior to root canal obturation has an inhibitory effect on corono-apical penetration of bacteria. 93 single rooted teeth were instrumented and sterilized with ethylene oxide. They were assigned to three control groups and four test groups with n = 20 each. For one week, they were dressed with different medicaments: The first group with a 5% chlorhexidine gel, the second with Ledermix, the third with a fresh mix of calcium hydroxide and water and the fourth without any medication. After obturation (lateral condensation, AH26) the roots were fixed between a top and a bottom chamber. The top chamber contained 3 mL trypticase soy broth with 10(8) Staphylococcus epidermidis CFU's/mL, whereas the bottom chamber contained sterile trypticase soy broth. For one year, the mounts were incubated at 37 degrees C. They were checked on a regular basis for turbidity in their bottom chambers indicating bacterial growth. None of the test samples leaked for three months. After one year, the calcium hydroxide group had only 6 leaking samples whereas the chlorhexidine group had 14, the Ledermix group 15, and the unmedicated group had 13 leaking samples. It may be concluded that under the conditions of this study, calcium hydroxide was the medicament of choice to avoid bacterial penetration of the root canal. Ledermix did not perform better than no premedication. Chlorhexidine was superior to Ledermix in the second third of the observation period.

A dentin-bonding root canal sealer (ZUT) has been developed, consisting of an experimental glass ionomer cement (KT-308) and an antimicrobial silver-containing zeolite (0.2% by weight). This in vitro study evaluated the ability of ZUT used with or without gutta-percha, to resist bacterial ingress of Enterococcus faecalis over a period of 90 days. Canals of 80 single-rooted teeth were prepared with apical patency and filled as follows (n = 10): KT-308 alone; KT-308 with a single gutta-percha cone (SCGP); ZUT alone; ZUT with SCGP; AH26 alone; AH26 with SCGP; positive control-no root canal filling; and negative control-no root canal filling, with the apices of this group sealed with C&B Metabond cement. Teeth were coated with nail polish except for the apical 2 mm, and each tooth was sealed in a 4-ml glass vial, with an 18-gauge needle inserted through the vial cover and bonded into the pulp chamber with C&B Metabond cement. After sterilization with 2.5 Mrad gamma-radiation, Brain Heart Infusion broth with phenol red was injected into each vial. An inoculum of E. faecalis was pipetted through the needle into the pulp chamber every 5 days, and the broth was monitored daily for color change and turbidity. When change occurred, the broth was cultured for growth of E. faecalis. Kaplan-Meier survival analysis and the log-rank test revealed no significant differences among the three sealers used. The presence of gutta-percha, however, significantly improved resistance to bacterial ingress through obturated root canals (X, p < 0.05). Under the conditions of this study, the hypothesized advantage of ZUT (0.2% zeolite) was not demonstrated.

Aim: The purpose of this study was to evaluate the effects of smear layer and canal instrumentation on leakage in root-filled teeth., Methodology: Six groups (n = 12) of freshly extracted human canines and premolars with closed apices and single roots were used. Groups A, B, C, and D were instrumented with engine-driven rotary nickel-titanium MCXIM files and Groups E and F were instrumented with conventional stainless steel hand files. Groups A, C, and E were flushed with 3.0 mL of 17.0% REDTA to remove the smear layer prior to obturation. All teeth were flushed with 5.25% NaOCl, then obturated with AH-26 sealer and either the lateral condensation (Groups C-E) or thermomechanical compaction technique (Groups A and B). Copper wire was placed coronally in contact with the gutta-percha in each tooth and, after immersion in 0.9% NaCl solution, a 10 volt dc voltage was connected between each tooth and a stainless steel electrode. The current flow in the circuit was observed for 45 days. One way ANOVA and Duncan's Multiple Range Test were used to compare Groups A-F at time intervals of 10, 20, 30 and 45 days and identify statistically significant differences., Results: Significantly less microleakage occurred when the smear layer was removed and when the canals were obturated with thermoplasticized gutta-percha. Canals instrumented with engine-driven NiTi files exhibited less leakage than hand-instrumented canals irrespective of obturation method., Conclusions: Smear layer removal is beneficial to root canal sealing. Obturation with thermoplasticized gutta-percha provides a superior seal whilst canal instrumentation with engine-driven NiTi files reduces the extent of microleakage in root canals.

Forty extracted maxillary central incisors were instrumented at the working length to a #50 file. The roots were sectioned transversely with a diamond disk at 7 mm from the anatomical apex. At the opening of the root canal of each section, hemicircular cavities were drilled with a specially designed bur. The corresponding root sections were cemented with glue, thus obtaining root canals with similar cavities that simulated internal resorptions. Teeth were embedded in plaster casts to facilitate their handling. The specimens were randomly separated into four groups of 10. The following obturation techniques were evaluated: lateral compaction (group A), hybrid technique (group B), Obtura II (group C), and Thermafil (group D). AH26 was used as the sealer. After obturation, the plaster was removed and the teeth were radiographed in buccolingual and mesiodistal directions to evaluate the quality of the obturation at the IRC. The incisors were then cut with a scalpel at the same level as the previous section, to examine, under a stereomicroscope, the type of material that filled the IRC. Obtura II gave the best results and in most of the specimens obturated with this technique, the IRC were filled mainly with gutta-percha. Statistical analysis of the data indicated that the differences between group C and the other groups were significant (P < 0.05).

Occurrence of apical transportation (AT) may complicate the root filling procedure and result in a compromised seal. In part I of this study, human mandibular premolars with single, curved (21 to 39 degrees), or straight canals were prepared by Lightspeed or a step-back hand filing technique. An AT index was determined using a double exposure radiographic technique. The prepared canals were obturated using lateral condensation of gutta-percha. Leakage along the apical 3 mm of root filling was measured with a fluid transport model. After hand filing, AT and perforation occurred in 87% of the curved canals. The AT indices were > or = 0.4 mm. After Lightspeed preparation, AT occurred in only 19% of the curved canals. The hand filing/curved group leaked statistically significantly more than the hand filing/straight and Lightspeed/curved groups (p = 0.002). We conclude that occurrence of AT is a factor that negatively influences the apical seal when curved canals are obturated by lateral condensation of gutta-percha.