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.

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.

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.

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.

Occupational dermatitis in health care workers evaluated for suspected allergic contact dermatitis.

BACKGROUND: Contact dermatitides occur commonly among health care workers (HCWs). OBJECTIVE: To contrast the atopic status and incidence, location, and final diagnosis of skin diseases afflicting HCWs versus non-HCWs (NHCWs) evaluated for suspicion of allergic contact dermatitis (ACD); and among the population diagnosed with ACD, to compare the incidence and occupational relatedness of allergens found in HCWs with the rates observed in NHCWs. METHODS: Between July 1, 1994, and May 30, 2014, 2611 patients underwent patch testing by the senior author. Of these, 165 were classified as HCWs based on their primary occupation. Statistical analysis was done using a χ test. RESULTS: Health care workers were more likely than NHCWs to be women and to have hand dermatitis. Women, but not men, HCWs suffered more irritant contact dermatitis. Health care workers had significantly more work-related ACD, especially to formaldehyde, quaternium-15, 2-bromo-2-nitropropane-1,3-diol, cocamide diethanolamine (DEA), thiuram mix, carba mix, thimerosal, benzalkonium chloride, glutaraldehyde, and bacitracin. LIMITATIONS: Only patients suspected of having ACD were tested. Our population was geographically limited to metropolitan Kansas City, MO and metropolitan New York, NY. CONCLUSIONS: Health care workers suffer more from occupational ACD, especially of the hands, than do NHCWs, including to allergens not present on available standard allergen series.

North American contact dermatitis group patch test results: 2011-2012.

BACKGROUND: Patch testing is an important diagnostic tool for assessment of allergic contact dermatitis (ACD). OBJECTIVE: This study documents the North American Contact Dermatitis Group (NACDG) patch-testing results from January 1, 2011, to December 31, 2012. METHODS: At 12 centers in North America, patients were tested in a standardized manner with a series of 70 allergens. Data were manually verified and entered into a central database. Descriptive frequencies were calculated, and trends analyzed using χ statistics. RESULTS: Four thousand two hundred thirty-eight patients were tested; of these, 2705 patients (63.8%) had at least 1 positive reaction, and 2029 (48.0%) were ultimately determined to have a primary diagnosis of ACD. Four hundred eight patients (9.6%) had occupationally related skin disease. There were 7532 positive allergic reactions. As compared with previous reporting periods (2009-2010 and 2000-2010), positive reaction rates statistically increased for 6 allergens: methylchloroisothiazolinone/methylisothiazolinone (5.0%; risk ratios [RRs]: 2.01 [1.60-2.52], 1.87 [1.61-2.18]), lanolin alcohol (4.6%; RRs 1.83 [1.45-2.30], 2.10 [1.79-2.47]), cinnamic aldehyde (3.9%; 1.69 [1.32-2.15], 1.53 [1.28-1.82]), glutaral (1.5%; 1.67 [1.13-2.48], 1.31 [1.00-1.71]), paraben mix (1.4%; 1.77 [1.16-2.69], 1.44 [1.09-1.92]), and fragrance mix I (12.1%; RRs 1.42 [1.25-1.61], 1.24 [1.14-1.36]). Compared with the previous decade, positivity rates for all formaldehyde-releasing preservatives significantly decreased (formaldehyde 6.6%; RR, 0.82 [0.73, 0.93]; quaternium-15 6.4% RR 0.75 [0.66, 0.85]; diazolidinyl urea 2.1%; RR, 0.67 [0.54, 0.84]; imidazolidinyl urea 1.6%, 0.60 [0.47, 0.77]; bronopol 1.6%; RR, 0.60 [0.46, 0.77]; DMDM hydantoin 1.6%; RR, 0.59 [0.54, 0.84]). Approximately a quarter of patients had at least 1 relevant allergic reaction to a non-NACDG allergen. In addition, approximately one-fourth to one-third of reactions detected by NACDG allergens would have been hypothetically missed by T.R.U.E. TEST (SmartPractice Denmark, Hillerød, Denmark). CONCLUSIONS: These data document the beginning of the epidemic of sensitivity to methylisothiazolinones in North America, which has been well documented in Europe. Patch testing with allergens beyond a standard screening tray is necessary for complete evaluation of occupational and nonoccupational ACD.

Contact dermatitis caused by preservatives.

Preservatives are biocidal chemicals added to food, cosmetics, and industrial products to prevent the growth of microorganisms. They are usually nontoxic and inexpensive and have a long shelf life. Unfortunately, they commonly cause contact dermatitis. This article reviews the most important classes of preservatives physicians are most likely to encounter in their daily practice, specifically isothiazolinones, formaldehyde and formaldehyde-releasers, iodopropynyl butylcarbamate, methyldibromoglutaronitrile, and parabens. For each preservative mentioned, the prevalence of sensitization, clinical presentation of contact dermatitis, patch testing concentrations, cross reactions, and related legislation will be discussed. Mandatory labeling of preservatives is required in some countries, but not required in others. Until policies are made, physicians and patients must be proactive in identifying potential sensitizers and removing their use. We hope that this article will serve as a guide for policy makers in creating legislation and future regulations on the use and concentration of certain preservatives in cosmetics and industrial products.

Methenamine: a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era.

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.

Contact sensitivity to preservatives in Singapore: frequency of sensitization to 11 common preservatives 2006-2011.

BACKGROUND: Preservatives are indispensable agents used to prevent bacterial and fungal contamination of cosmetics, personal care products, domestic preparations, and industrial products. OBJECTIVE: We evaluated patch-test data at the National Skin Centre, Singapore, from 2006 to 2011 to identify the trends in preservative contact allergies. METHODS: All patients with suspected contact dermatitis were patch tested to 4 preservatives within the modified European standard series. Patients were also tested with 7 preservatives from our special series if clinically indicated. RESULTS: Three thousand one hundred seventy-seven patients were tested to preservatives in the standard series. Sensitization frequencies were all greater than 1%: parabens (2.58%), methylchloroisothiazolinone/methylisothiazolinone (1.75%), quaternium 15 (1.43%), and methyldibromoglutaronitrile (1.2%). There was no change in trends in sensitization frequencies from 2006 to 2011, with no increase in sensitization frequency to methylchloroisothiazolinone/methylisothiazolinone. The sensitization frequencies for methyldibromoglutaronitrile/phenoxyethanol and diazolidinylurea were 2.03% and 1.37%, respectively, and remained less than 1% for bronopol, imidazolidinyl urea, and 2-phenoxyethanol. A rate of 0% was seen for 1,3-dimethylol-5,5-dimethyl hydantoin and formaldehyde; 9.4% of positive patch-test results became positive only at day 7. CONCLUSIONS: Preservatives are common causes of allergic contact dermatitis. This should be considered when introducing new preservatives into the market. Day 7 readings are important to detect late reactions.

Contact sensitization to cosmetic series of allergens in a general population in Beijing.

Cosmetic allergic contact dermatitis (CACD) due to common cosmetic allergens in standard series has been extensively studied; however, the prevalence of contact allergy to other cosmetic allergens other than those in standard series is largely unknown. In this study, the frequency of contact sensitization to a European cosmetic series of allergens (Chemotechnique Diagnostics, Vellinge, Sweden) in healthy university student volunteers were detected in Beijing. Of 201 students studied, fifty-eight exhibited positive results, and 9 of them reported had cosmetics related dermatitis previously. The total positivity rate was not correlated to gender. The leading allergens were thimerosal (19.4%), shellac (3.0%), cocamidopropyl betaine (2.0%), hexamethylenetetramine (1.5%), dodecyl gallate (1.5%), hexahydro-1,3,5-tris-(2-hydroxyethyl)triazine (1.0%) and methyldibromo glutaronitrile (1.0%). The positivity rate of thimerosal patch test in men (9.8%) was lower than that of women (23.6%, P < 0.05, Chi square test), but no difference could be found between the prevalence of other cosmetic allergens in men and women (P > 0.05, Chi square test). These results suggested that some cosmetic-related contact allergies may be missed by just testing patients with the European standard series or T.R.U.E. test system only, we recommend shellac, cocamidopropyl betaine, hexamethylenetetramine and dodecyl gallate as the additionally candidates for patch testing in patients with suspected CACD.

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.

The reversible cerebral vasoconstriction syndrome in association with venlafaxine and methenamine.

The reversible cerebral vasoconstriction syndrome (RCVS) is characterised by thunderclap headache and multifocal vasoconstriction of cerebral arteries on angiography. It is often drug induced, but it can occur postpartum, and as a result of a number of other precipitants. To make the diagnosis, it is necessary to exclude other causes of severe headache (such as aneurysmal subarachnoid haemorrhage, carotid dissection and primary angiitis of the central nervous system). However, it is also important to show that the vasoconstriction has resolved with repeat angiography at the 3-month stage. Here we report two cases of RCVS in association with venlafaxine and the urinary antiseptic, methenamine. Serotonin-norepinephrine reuptake inhibitors have recently been reported as a possible precipitant, but this is the first report to implicate methenamine. Although RCVS is relatively uncommon, it should be considered in the differential of those presenting with thunderclap headache.

Allergic contact dermatitis of the vulva.

BACKGROUND AND OBJECTIVES: Allergic contact dermatitis (ACD) of the vulva arises as a primary condition or develops secondary to topical agents. We aimed to describe the incidence of ACD in patients presenting with vulvar symptoms and to identify the allergens of most importance. PATIENTS AND METHODS: Using a database of the patch testing results from 3 geographically distinct sites, we identified patients tested to a gynecologic series between 2003 and 2010. Patients had patch testing to the standard European battery and a gynecologic series. Patch testing was in line with accepted universal methods: application on day 1, allergen removal and initial reading on day 3, and final reading on day 5. RESULTS: Ninety patients were included. Thirty-five (39%) had a relevant positive result. The 5 allergens with the highest number of cases with a relevant reaction were natural fragrance mix 2%, balsam of Peru, benzocaine 5%, fragrance mix 8%, and quaternium 15 1%. The most common gynecologic series allergen to cause a relevant reaction was terconazole. CONCLUSIONS: Allergic contact dermatitis is a frequent finding in patients presenting with vulvar symptoms. We identified a relevant positive result to patch testing in 39%. We found fragrances, medicaments, and preservatives to be of most relevance.

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.

Urinary tract analgesics for the treatment of patients with acute cystitis: where is the clinical evidence?

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.

Is quaternium-15 a formaldehyde releaser? Correlation between positive patch test reactions to formaldehyde and quaternium-15.

BACKGROUND: The question of whether quaternium-15 is a formaldehyde releaser is controversial. Understanding this relationship is critical because of the widespread use of quaternium-15 and the need to properly advise formaldehyde-allergic individuals. OBJECTIVES: This study aimed to look for an association between allergy to quaternium-15 and formaldehyde by correlating reactions to both and to correlate the intensity of positive patch test results to formaldehyde with reactivity to quaternium-15. METHODS: This is a retrospective analysis of 1905 patients who underwent patch testing for allergic contact dermatitis. Associations were analyzed by χ testing. RESULTS: Of all patients, 9.5% reacted to quaternium-15, 7.2% reacted to formaldehyde, and 5.4% reacted to both (P < 0.001). Of 137, 86 had strong (2 or 3+) and 51 had weak (1+ or +/-) formaldehyde reactions; there was no relationship between the severity of formaldehyde reactivity and responsiveness to quaternium-15 (P = 0.229). Sex analysis did not change these findings. LIMITATIONS: This study is limited by its retrospective analysis and small sample size. CONCLUSIONS: A statistically significant relationship exists between reactivity to quaternium-15 and formaldehyde; however, the severity of the formaldehyde reaction does not predict reactivity to quaternium-15. Despite coreactivity with formaldehyde, quaternium-15 may not be a significant formaldehyde releaser. The coreactivity between quaternium-15 and formaldehyde requires further studies.

Occupational contact dermatitis in painters: an analysis of patch test data from the Danish Contact Dermatitis Group.

BACKGROUND: Painters are among the occupational groups that most commonly experience occupational contact dermatitis, but few investigations exist concerning this occupation. OBJECTIVES: To characterize painters with contact dermatitis and identify the most common allergens associated with the occupation. Materials and methods. All patch test results of 219 painters and 1095 matched controls registered by the Danish Contact Dermatitis Group between 2001 and 2010 were analysed. RESULTS: Hand eczema (p < 0.0001) and occupational contact dermatitis (p < 0.0001) were observed significantly more often in the painters than in the group of controls. Sensitizations to the following allergens from the European baseline series were associated with the occupation and were statistically significant: methylchloroisothiazolinone/methylisothiazolinone, epoxy resin, formaldehyde, and quaternium-15. Three different isothiazolinones emerged as the most frequent sensitizers of the allergens tested in addition to the baseline series. CONCLUSIONS: The results indicate that painters have an increased risk of developing occupational hand eczema. Isothiazolinones and epoxy resin proved to be the two most frequent sensitizers in painters.

Non-fragrance allergens in specific cosmetic products.

OBJECTIVES: Reports about the nature of the ingredients responsible for allergic contact dermatitis caused by specific cosmetic products are scarce. METHODS: Between January 2000 and December 2010, the specific cosmetic products having caused allergic contact dermatitis, as well as the individual allergenic cosmetic ingredients present in them, were recorded by use of a standardized form. RESULTS: Among 11 different categories of cosmetic product, skin care products, followed by hair care and body-cleansing products, were most often involved. The presence of the allergenic ingredient(s) in a specific cosmetic product was confirmed according to the ingredient label in 959 of 1448 records. Six hundred and twenty-one of 959 concerned non-fragrance components, preservatives being responsible for 58% of them. Reactions to formaldehyde and formaldehyde-releasers were most often correlated with body-cleansing products, particularly 2-bromo-2-nitropropane-1,3-diol and skin care products. They were followed by the methylchloroisothiazolinone/methylisothiazolinone mixture, most frequently found as allergens in hair care and intimate hygiene products, and facial cleansers (in the last category together with diazolidinyl urea). Octocrylene was by far the most frequent (photo)allergen in sun care products. CONCLUSIONS: This study provides information on the presence and frequency of allergens in specific causal cosmetic products.