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

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

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

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

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

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

Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study.

BACKGROUND: Recurrent urinary tract infections (UTI) are an important cause of morbidity and mortality in renal transplant recipients (RTR). METHODS: In this retrospective study we gathered clinical data from patients prescribed methenamine hippurate to prevent recurrent UTI pre- and post-intervention. Thirty-eight RTR ≥18 years old at Northwestern Memorial Hospital from 2006-2017 were included in the final analysis. RESULTS: The median and range for follow-up days were 365 (299-365) pre- vs 314 (105-365) post-methenamine. Total UTI frequency (9.16 vs 5.01/1000 patient follow-up days), days of antibiotic therapy to treat UTI (215 vs 132/1000 patient follow-up days), and hospitalization due to UTI (2.64 vs 1.07/1000 patient follow-up days) decreased while patients took methenamine. Escherichia coli and Klebsiella pneumoniae were the most commonly identified cause of UTI both pre- and post-intervention. Drug resistant bacteria (ESBL-producing or VRE) affected 3 patients pre- and recurred in 1 of those patients plus 3 new patients post-methenamine. Methenamine had few adverse side effects for patients. One patient had nausea and 1 was intolerant. CONCLUSION: We found that methenamine is well tolerated and is useful in reducing UTI, antibiotic prescriptions, and hospitalization in RTR with recurrent UTI. Larger prospective studies are needed to confirm these findings.

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

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

Allergic contact dermatitis related to homemade slime: a case and review of the literature.

Slime has become extremely popular as a children's toy in recent years and is typically made with various household substances. Although reports of slime causing skin irritation are not uncommon, case reports of slime-induced allergic contact dermatitis have only recently surfaced. We present a case of a child with hand dermatitis, history of exposure to slime, and positive allergen patch testing to two ingredients found in slime. The case underscores the need for clinicians to be aware of slime as a possible cause of allergic contact dermatitis in children. Given the trend of newly-reported cases, we briefly review the current literature to date.

Lower urinary tract infections in women.

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

Evaluation of Functionality and Biological Responses of Mytilus galloprovincialis after Exposure to Quaternium-15 (Methenamine 3-Chloroallylochloride).

Although the irritant effects of quaternium-15 have been established, little is known about the toxicological consequences induced by this xenobiotic on aquatic invertebrates. The present article reports toxicological, histological and physiological effects of quaternium-15 following the exposure of Mytilus galloprovincialis for 18 days at three different concentrations (0.1, 1.0 and 2.0 mg/L). The results demonstrate that at higher concentrations histological damages to M. galloprovincialis gills occur, like melanosis, light exfoliations, increase of mucus production and infiltrative inflammation. In addition digestive gland cells of M. galloprovincialis, were not able to perform the regulation volume decrease (RVD) owing to osmotic stress following the exposure to the preservative. Overall, this first study on quaternium-15 highlights that it can jeopardize both the morphology and vital physiological processes in marine invertebrates, depending on the duration of exposure and the concentration of the preservative, indicating that further studies are necessary to increase our knowledge about the effects of this substance, commonly added to our products of daily use.

Contact Dermatitis, Patch Testing, and Allergen Avoidance.

In patients presenting with a complaint of rash, contact dermatitis is often the underlying diagnosis making it an entity with which health care providers should be familiar. Contact dermatitis can be divided into irritant contact dermatitis and allergic contact dermatitis. In a patient suspected of having allergic contact dermatitis, patch testing can be done to identify specific allergens. Education focused on allergen avoidance and safe products is an integral part of treatment for the contact dermatitis patient. Knowledge of the most common allergens is helpful for clinicians to be able to provide this education.

Cutaneous delayed-type hypersensitivity in patients with atopic dermatitis: reactivity to topical preservatives.

BACKGROUND: Patients with atopic dermatitis (AD) have chronic dry skin to which they frequently apply skin care products containing preservatives, and they are predisposed to developing cutaneous delayed-type hypersensitivity. OBJECTIVE: We sought to compare the rates of positive patch test reactions to allergens on the North American Contact Dermatitis Group (NACDG) standard tray among patients with and without AD and to assess whether atopic patients in our database were more likely to patch test positive to preservatives. METHODS: A total of 2453 patients underwent patch testing to the NACDG standard screening series. The incidence of positive patch test reaction among patients with AD (n = 342) and without AD (n = 2111) was assessed. Statistical analysis was done using a χ(2) test. RESULTS: Compared with nonatopic patients, patients with AD were statistically more likely to have positive patch tests. AD was associated with contact hypersensitivity to quaternium-15, imidazolidinyl urea, DMDM hydantoin, and 2-bromo-2-nitropropane-1,3-diol but not to parabens, formaldehyde, or diazolidinyl urea. LIMITATIONS: Only patients suspected of having allergic contact dermatitis were tested. Our population was geographically limited to metropolitan Kansas City, MO, and metropolitan New York City, NY. CONCLUSIONS: Patients with AD should avoid the use of skin care products preserved with formaldehyde releasers.

Patch testing for allergic contact dermatitis to cigarettes: smoked/unsmoked components and formaldehyde factors.

A patient with hand dermatitis reported that switching her smoking hand resulted in reduced symptoms. When allergy to cigarettes is suspected the literature supports standard allergy testing as well as testing the individual components of cigarettes. Initial standard patch testing revealed an allergy to formaldehyde and the formaldehyde releasing agent, quaternium-15. The patient did not react to her usual roll-your-own cigarette components but reacted to the smoked filter paper of a particular brand of cigarette she frequently borrowed from a friend. Possible explanations include either a variation of ingredients between cigarettes that alters the formaldehyde concentration or another unidentified allergen in the branded cigarette causing allergic contact dermatitis.

Evaluating quaternium-15 effects on Mytilus galloprovincialis: New insights on physiological and cellular responses.

Among personal care products, quaternium-15 is prominently featured as a preservative in items such as shampoos, soaps, shaving products, and cosmetics. The widespread use of these products in people's daily routines contributes to quaternium-15 release into aquatic ecosystems. In this context, the primary aim of the study was to assess the physiological and cellular responses of the digestive gland and gills in Mytilus galloprovincialis to quaternium-15 exposure. Cell viability and the ability of digestive gland cells to regulate their volume were evaluated. Additionally, the expression of the genes involved in oxidative stress response was assessed to further substantiate the compound's harmful effects. Results indicated a significant decrease in both the viability of digestive gland cells and their RVD (regulatory volume decrease) capacity when exposed to a hypotonic solution. Furthermore, impairment of digestive gland cell function was corroborated by the modulation of oxidative stress-related gene expression, including SOD, Cat, as well as Hsp70 and CYP4Y1. Similar gene expression alterations were observed in the gills, reflecting impaired functionality in this vital organ as well. In summary, the outcomes of the study provide conclusive evidence of the toxicity of quaternium-15. This underscores the urgent need to further investigate the toxicological effects of this contaminant on aquatic ecosystems and emphasises the necessity of limiting the use of products containing quaternium-15.

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

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

Patch testing with 2.0% (0.60 mg/cm 2) formaldehyde instead of 1.0% (0.30 mg/cm 2) detects significantly more contact allergy.

BACKGROUND: The currently used patch test concentration for formaldehyde is 1.0% (wt/vol) in water. However, clinical experience and previous studies suggest that 1.0% might be insufficient for detecting an optimized number of clinically relevant cases of contact allergy to formaldehyde. OBJECTIVES: To validate earlier patch test results for comparison of 1% (wt/vol) and 2% (wt/vol) formaldehyde in water, and to investigate co-reactivity with quaternium-15. MATERIALS AND METHODS: In 12 dermatology clinics, 3591 patients were routinely patch tested simultaneously with 2.0% (wt/vol) (0.60 mg/cm(2)) and 1.0% (wt/vol) (0.30 mg/cm(2)) formaldehyde. Micropipettes were used for delivering the exact dosage of the allergen. RESULTS: Significantly more patients reacted to 2.0% formaldehyde than to 1.0% (3.4% versus 1.8%, p < 0.001). Overall, there were no sex differences between those reacting positively to 2.0% and 1.0%. Of 25 quaternium-15-positive patients, 4 (0.1%) reacted positively without reacting to formaldehyde. CONCLUSION: On the basis of the results of this multicentre study, as well as of previous studies, it can be suggested that 2.0% (wt/vol) in water formaldehyde should be used in routine patch testing in the baseline series.

The triggering role of allergic contact dermatitis in discoid lupus erythematosus.

BACKGROUND: The onset and exacerbations of discoid lupus erythematosus (DLE) can be precipitated by several factors like needling, scratches, trauma, X-rays, heat, cold, pressure, tattooing, scars, allergic and irritant dermatitis and inflammatory dermatoses. OBJECTIVE: To investigate the role of allergic contact dermatitis (ACD) in devolopment and triggering of the lesions of DLE. MATERIALS AND METHODS: This study was performed on 30 patients with DLE. European baseline series and cosmetic patch test series were used. At least 1+ reaction was accepted as meaningful. RESULTS: Twenty-three (76.7%) of 30 DLE patients and 16 (40%) of 40 control group patients were allergic to at least one allergen on standard patch test series. The difference between the groups were found statistically significant. Seventeen (56.7%) of 30 DLE patients and 6 (15%) of 40 control group patients were allergic to at least one allergen on cosmetic patch test series. The difference between the groups were statistically significant. The most sensitized allergens in both the groups were nickel sulphate, paraphenylen diamine, potassium dichromate from standard patch test series; quaternium 15, cocamidopropyl betain from cosmetic patch test series, in order. CONCLUSION: This study is distinctive since it is the first study to determine the eliciting role of ACD on DLE by imposing standard and cosmetic patch test series on DLE and control group patients. Worldwide, there is no study based on this subject. In the DLE group, the results of sensitization on standard and cosmetic patch test series were higher and statistically significant. Larger studies are required to reveal the exact role.

Positive patch test reactions in older individuals: retrospective analysis from the North American Contact Dermatitis Group, 1994-2008.

BACKGROUND: Relatively little is known about the epidemiology of allergic contact dermatitis in older individuals. OBJECTIVES: We sought to determine the frequency of positive and clinically relevant patch test reactions in older individuals (≥ 65 years old) referred for patch testing, and to compare these results with those of adults (≤ 64-19 years) and children (<18 years). DESIGN: This was a retrospective cross-sectional analysis of North American Contact Dermatitis Group data from 1994 to 2008. RESULTS: A total of 31,942 patients (older n = 5306; adults n = 25,028; children n = 1608) were patch tested. The overall frequency of at least one allergic reaction in older individuals was 67.3% as compared with 66.9% for adults (P = .5938) and 47% for children (P = .0011). Reaction rates that were statistically higher in older individuals as compared with both adults and children included: Myroxylon pereirae, fragrance mix I, quaternium-15, formaldehyde, imidazolidinyl urea, diazolidinyl urea, neomycin, bacitracin, methyldibromo glutaronitrile, methyldibromo glutaronitrile/phenoxyethanol, ethyleneurea melamine formaldehyde mix, and carba mix (P values < .0004). Patch test reaction rates that were significantly lower in older individuals than both comparison groups included: nickel, thimerosal, and cobalt (P values < .0001). LIMITATIONS: Referral population was a limitation. CONCLUSIONS: Older individuals were more likely to have at least one positive patch test reaction as compared with children, but had similar rates to adults. The frequency of positive reactions to specific allergens differed by age group, most likely as a result of exposures.