Urinary tract disorders
Henry J. Woodford in Essential Geriatrics, 2022
Improving the hydration of care home residents seems to reduce the incidence of UTI diagnosis.66 This may reflect issues regarding misdiagnosis of UTI, i.e. wrongly suspected due to dark/pungent urine and a non-specific functional decline caused by dehydration, in this vulnerable group. Methenamine has an antiseptic action via formaldehyde formation in urine with pH < 6. However, there is very limited data available regarding the prevention of UTI in older people. Two RCTs performed in adults (mean age around 60) over 40 years ago suggested a reduction in bacteriuria but not symptomatic UTI or antibiotic usage.67 D-mannose is a sugar that could provoke protein glycosylation and the subsequent inhibition of bacterial adherence to uroepithelial cells. It has been compared to nitrofurantoin or nothing in women with recurrent UTI (n = 308; median age 49; six-month follow-up).62 A similar benefit was found for reducing UTI recurrence compared to nitrofurantoin, both of which were better than nothing. Over 75% of infections were due to E. coli. Diarrhoea occurred in 8%. Drug adverse effects were most common with nitrofurantoin, where at least one adverse effect occurred in 27% of people. Limitations of the study include the lack of a placebo and all participants received a week of ciprofloxacin at start of study. Finally, cranberry juice has also been tried. However, a recent systematic review of available data did not support the use of cranberry products to prevent UTI.68
Methenamine Mandelate and Methenamine Hippurate
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Methenamine was introduced into clinical practice as a urinary antiseptic as long ago as 1894. The antiseptic action of this cyclic hydrocarbon depends on its chemical breakdown by hydrolysis to formaldehyde and ammonia. This process takes place in the urine, to a significant degree only when the urine is acidic. In vitro studies have suggested that an effective concentration of formaldehyde with recommended doses is likely to be achieved only if the urine pH is less than 5.7–5.85 (Musher and Griffith, 1974). The drug is thereby entirely dependent for its effect on proper acidification of the urine (Kass, 1955). Formaldehyde is not released while methenamine circulates in the blood.
M
Caroline Ashley, Aileen Dunleavy, John Cunningham in The Renal Drug Handbook, 2018
Under acid conditions methenamine is slowly hydrolysed to formaldehyde and ammonia. Almost no hydrolysis of methenamine takes place at physiological pH, and it is therefore virtually inactive in the body. Methenamine is rapidly and almost completely eliminated in the urine, and provided this is acidic (preferably below pH 5.5) bactericidal concentrations of formaldehyde occur. Because of the time taken for hydrolysis, however, these do not occur until the urine reaches the bladder.
Formaldehyde as an alternative to antibiotics for treatment of refractory impetigo and other infectious skin diseases
Published in Expert Review of Anti-infective Therapy, 2019
Philip Nikolic, Poonam Mudgil, John Whitehall
Formaldehyde is the simplest aldehyde and exists as a colorless gas with a strong odor at room temperature. It was first synthesized in 1855 and is used for a variety of roles. This includes in embalming, the manufacture of particle-board, plywood, and other wooden furniture products and as a preservative in products such as cosmetics and medicinal creams [8]. When used as a preservative it is used as an aqueous solution of 37%-50% formaldehyde called formalin [9]. Formaldehyde is used as a preservative due to its genotoxicity to bacteria and fungi. It is capable of binding to DNA and proteins to cause DNA-DNA cross-links, DNA-protein cross-links, irreversible formaldehyde adducts as well as other forms of DNA and protein damage [10,11]. It is effective against bacteria at very low concentrations with the MIC of formaldehyde against S. aureus being only 156 mg/L or 0.02% [12]. Formaldehyde has also been used to treat bacterial infections in the form of the antibiotic methenamine. Methenamine is an antibiotic that was used to treat urinary tract infections but has since become a ‘forgotten drug’. It exerts its antibacterial activity by releasing formaldehyde in acidic environments and is capable of bactericidal activity at concentrations greater than 25 µg/ml [13].
Prescription of antibiotics for urinary tract infection in general practice in Denmark
Published in Scandinavian Journal of Primary Health Care, 2019
Anne Holm, Gloria Cordoba, Rune Aabenhus
Another weakness of our study is the lack of an officially recognized guideline for treatment of UTI in general practice. Nonetheless, the available guidelines were in relatively good accordance since all of them recommended using pivmecillinam in most cases of acute UTI. However, sulfamethizole remained the drug of choice in the Northern region of Denmark. Recommendations for prevention of acute UTI were not completely consistent either. The two guidelines that mentioned this indication both recommended trimethroprim, but one still recommended nitrofurantoine as the alternative choice and the other recommended pivmecillinam. Also, we were unable to determine if antibiotics treatment was appropriate due to the lack of clinical data in the database. Methenamine was used quite extensively for prevention of UTI in the elderly despite no guidelines mentioning this drug. Little research exists on the use of methenamine for prevention of UTI, but a Cochrane review has shown promising results [19]. The use of nitrofurantoine for treatment of acute UTI was also higher than what would be expected from guideline recommendations. This may be appropriate since nitrofurantoine has low resistence rates even in countries with higher use [20].
Preventive effect of methenamine in women with recurrent urinary tract infections – a case–control study
Published in Scandinavian Journal of Primary Health Care, 2022
Linda Rui, Morten Lindbaek, Svein Gjelstad
A 2012 Cochrane review on methenamine examined the effects and advantages of methenamine for the prevention of UTIs [16]. Thirteen studies with 2032 participants met the inclusion criteria. Six trials with a total of 654 patients reported on symptomatic UTIs, eight trials involving 796 patients reported the effects on bacteriuria, and one reported both outcomes. No studies were found on the longstanding use of methenamine for the prevention of recurrent UTI. In that review, subgroup analyses indicated that methenamine may have efficacy in patients without urinary or kidney abnormalities. For example, for the short-term treatment [≤1 week], a reduction in the number of symptomatic UTIs was found in patients without urinary or kidney abnormalities. The authors concluded that methenamine may be effective for the prevention of UTIs when used as a short-term treatment. The rates of adverse events for preventing UTIs are low [15], but more studies are needed to assess both the safety and efficacy of the preventive use of methenamine hippurate over the longer term [17–22].
Related Knowledge Centers
- Alkylation
- Ammonia
- Resin
- Sublimation
- Nitrogen
- Adamantane
- Formaldehyde
- Cryptand
- Quaternium-15
- Hippuric Acid