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Decreased incidence of urinary tract infections in patients with spinal cord injury: effect of methenamine.

This study was designed to determine the effect of methenamine on the frequency of urinary tract infections (UTI) in hospitalized patients after spinal cord injury. The study included 56 patients with neurogenic bladder dysfunction treated with intermittent catheterization. A group of 34 patients was treated with methenamine, 1g twice daily; the other group of 22 patients was the control group receiving no antimicrobial therapy. On a weekly basis urine samples from all patients were obtained for urinalysis and culture. A total of 500 urine samples were analyzed. The patients treated with methenamine had 23.4% positive urine cultures which was significantly lower than 57.5% in the untreated control group (p less than 0.001). Our data suggest that methenamine therapy is an effective prevention of UTI in paralyzed patients with neurogenic bladder dysfunction during the rehabilitation in hospital.

Bacteriuria↗

Value of urinary prophylaxis with methenamine in gynecologic surgery.

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.

Administration, Oral↗

Lack of effect of methenamine in suppression of, or prophylaxis against, chronic urinary infection.

Methenamine is frequently prescribed for patients who have chronic urinary infection to suppress bacterial growth during active infection or to prevent recurrence once an infection has been brought under control. We have examined the effect of methenamine mandelate and ascorbic acid on bacteriuria in para- and quadriplegics from a spinal cord unit. Patients with indwelling urinary catheters and those on a program of intermittent catheterization were included. No suppressive or prophylactic effect of this regimen was observed in any of our patients. Methenamine does not appear to be an effective antimicrobial agent in subjects who have an indwelling urinary catheter or in patients with spinal cord injury who are on intermittent catheterization. Since there appears to be reason to question the efficacy of methenamine in situations in which it is usually prescribed, evidence should be sought for a therapeutic effect in other cases. If no benefit is observed, the drug should not be used.

Ascorbic Acid↗

The use of Methenamine as an antiperspirant for amputees.

The socket of a prosthesis is a tightly closed container. Sweating inside the socket is annoying and may also irritate the skin over the stump or lead to local infection such as folliculitis. The most effective method of preventing sweating is by the use of astringent agents. Formaldehyde is a very strong astringent but is not pleasant to use and may cause skin irritation and systemic reactions. Methenamine, in water or when applied to the skin, decomposes to generate formaldehyde in small quantities which do not cause side effects. Methenamine was used on the stump of sixteen amputees. The trial was conducted as a double blind study using two different solutions market as solution A and as solution B. The effectiveness of the solutions as an antiperspirant was evaluated clinically by the subjects and the physician. Solution A containing Methenamine, was found significantly effective, both by the subjects and physician when compared with the solution B the blank one. The use of Methenamine as an antiperspirant is recommended in amputation stumps.

Administration, Topical↗

Topical methenamine therapy for hyperhidrosis.

Methenamine, in a gel stick formulation, effectively decreased palmar and plantar sweating in 24 of 26 individuals studied. All patients had essential hyperhidrosis and were evaluated in a double-blind, placebo-controlled study. Even though methenamine is believed to act by the slow release of formaldehyde, one patient, who had a formaldehyde sensitivity that was proved by a patch test, was able to use the methenamine gel stick without difficulty. Approximately one third of the patients experienced some continuing relief for one to three weeks after discontinuing the trial medication. I conclude that methenamine is a safe, effective addition to the available types of topical therapy for essential hyperhidrosis.

Administration, Topical↗

Methenamine as an induced artifact during extraction of formaldehyde-preserved tissue.

The effect of different basic drug assay procedures on the formation of artifactual methenamine from formaldehyde preserved and nonpreserved tissue was studied. Trichloroacetic acid was compared with ammonium sulfate as a protein precipitant and sodium hydroxide was compared with ammonium hydroxide as a pH modifier. The assay of nonpreserved tissue failed to result in the detection of methenamine. However, when preserved tissue was assayed by procedures which utilized ammonium compounds, large quantities of methenamine were detected using TLC and GC/MS. Trace quantities of methenamine were detected in extracts of preserved autolyzed tissue which was assayed using nonammonium compounds.

Animals↗

Effect of urinary acidifiers on formaldehyde concentration and efficacy with methenamine therapy.

Twenty-seven patients with indwelling urinary catheters and chronic bacteriuria were studied for methenamine efficacy. In a crossover fashion, each patient received methenamine mandelate granules 4 g/day alone, with ascorbic acid 4 g/day, and with ascorbic acid 4 g/day plus cranberry cocktail one 1/day. Proteus vulgaris, Pseudomonas aeruginosa, and E. coli were the common pathogens. Urinary acidifiers had no significant effect on mean urine pH, however, high urinary formaldehyde concentrations were associated with the use of ascorbic acid. Bacteriocidal formaldehyde levels were more frequently present in patients with acidic urine pH than those with alkaline pH. Although ascorbic acid increased formaldehyde levels, additional cranberry cocktail had no further effect. Despite higher formaldehyde levels, urine culture results were positive in most cases with or without urine acidification. Methenamine therapy may be of limited value in asymptomatic chronic bacteriuric patients with indwelling catheters.

Aged↗

Glycoconjugates in the cochlea as revealed by the silver methenamine method.

The glycoconjugates in the cochlea of the guinea pig were studied by staining samples by the silver methenamine method as well as after periodic acid-Schiff (PAS) staining. Results obtained by the two methods were similar but not identical. The silver methenamine method was much better in terms of resolution. However, this method of staining seemed less specific than the PAS reaction. When the silver methenamine method was used, the tectorial membrane and outer hair cells were specifically stained. Two types of fibrils were observed in the tectorial membrane. Thick fibrils were located in the fibrous layer. Thin fibrils were situated in the marginal band, the cover net, Hensen's stripe and the fibrous layer. The thick and thin fibrils appeared to correspond to type A and type B protofibrils, respectively. The outer hair cells were found to contain strongly stained particles which, presumably, consisted of glycogen. The basement membrane of the capillaries in the stria vascularis also gave a positive reaction, while that of other capillaries was essentially unstained. This finding suggests structural differences between these capillaries.

Animals↗

Glycoconjugates in the vestibular organs as revealed by the silver methenamine method.

The glycoconjugates in the vestibular organs of the guinea pig were studied after staining by the silver methenamine method and by the periodic acid-Schiff (PAS) reaction. The organic matrix of otoconia, otolithic membranes and cupulae were stained to the same degree by the PAS reaction. In contrast, the mineralizing and non-mineralizing matrices were clearly distinguished by the silver methenamine method. The otoconia were surrounded by an intensely stained organic matrix, while the otolithic membranes and cupulae were moderately stained. This histochemical difference suggests that the positively stained organic matrix of otoconia is not identical to the otolithic membranes and cupulae in terms of its biochemical composition. The strongly stained material may play an important role in turnover of calcium in otoconia. The contact areas between type I hair cell and nerve calyx were contained silver methenamine-positive material which is probably involved in adhesion of these cell membranes.

Animals↗

Evaluation of silver methenamine method for nanoleakage.

OBJECTIVES: The aim of this study was to evaluate nanoleakage patterns following silver methenamine staining of restorations bonded with a total-etch single bottle system, a self-etching primer system and a total-etch single bottle system after collagen depletion. METHODS: The dentin bonding systems used in this study were Prime and bond 2.1 (PB) and Clearfil SE Bond (CSEB). Cavities were made in grounded labial surfaces of 15 extracted bovine lower incisors, randomly divided into 3 Groups. Group 1 (PB), Group 2 (CSEB) and Group 3 (PB/SH) PB after collagen depletion with sodium hypochlorite (SH). The specimens were restored, sectioned and submitted to silver methenamine staining, polished and observed with low-vacuum back-scattered SEM. One way ANOVA and multiple-comparison Tukey's test were used for statistical analysis of the leakage scores. RESULTS: PB presented significantly greater silver deposition and a distinct pattern when compared to CSEB. No silver deposition was detected for PB after collagen depletion. SIGNIFICANCE: The dentine bonding systems tested were unable to prevent nanoleakage when used according to the manufacturers' instructions; however, CSEB presented a lower level of silver deposition. Collagen depletion prior to PB application may prevent nanoleakage occurrence in dentine walls. Silver methenamine staining may be a useful method for detection of nanoleakage in dentine when the collagen fibrils remain exposed within the hybrid layers.

Acetone↗

Determination of methenamine in biological samples by gas-liquid chromatography.

Methenamine (hexamethylenetetramine), a urinary disinfectant, was determined in human plasma and urine by gas-liquid chromatography with a short (10 m) open-bore glass capillary column (split ratio 1:20) and nitrogen-selective detector. An almost quantitative recovery (92.1%) was achieved by simple dilution of water-containing samples (0.5 ml) with acetone (4.5 ml). After centrifugation an aliquot (2 microliter) of the supernatant was injected into the gas chromatograph. Selectivity and sensitivity of the nitrogen detector allowed the quantitation of unchanged methenamine in plasma and urine up to 24 h after a single therapeutic dose of 1 g. Reproducibility of the method was 7.6 and 2.1% (C.V.) in serum and urine, respectively. The time required for the analysis of one sample was approx. 2 min. Due to the simple extraction and short analysis time it was possible to analyze the samples concurrently with sample taking. Absorption of standard tablets and an enterosoluble preparation of methenamine hippurate was compared.

Adult↗

Further observations on the potentiation of the antibacterial effect of methenamine by acetohydroxamic acid.

The use of methenamine in the treatment of urinary tract infections due to Proteus species is limited by urine alkalinity. Acetohydroxamic acid, an inhibitor of urease, maintains acidity despite growth of Proteus in urine. Easily achievable concentrations of acetohydroxamic acid in vitro systems that simulated the dynamics of the urinary tract potentiated the antibacterial effect of methenamine against Proteus species. The combined use of a urease inhibitor and methenamine may be effective in the treatment of urinary infection caused by these organisms.

Ammonia↗

Predictability of methenamine efficacy based on type of urinary pathogen and pH.

This study involved 27 geriatric patients with asymptomatic chronic bacteriuria; all had indwelling Foley catheters. The treatment regimens (daily oral dosage) were: methenamine mandelate (MM) granules, 4 gm; MM, 4 gm, plus ascorbic acid, 4 gm; and MM, 4 gm, plus ascorbic acid, 4 gm, plus cranberry cocktail, 1 liter--administered according to a cross-over design. Proteus vulgaris, Pseudomonas aeruginosa and E. coli were the most common urinary organisms. Proteus organisms were more often found in alkaline than in acidic urines, but the type of pathogen had no influence on urinary pH. Urinary formaldehyde concentration [HCHO] was lower in patients with Proteus infection (17.7 micrograms/ml) than in those with Pseudomonas (21.9 micrograms/ml) or E. coli infection (21.8 micrograms/ml). However, for Proteus infection, [HCHO] was higher in patients receiving MM plus ascorbic acid than in those receiving MM alone. Addition of cranberry cocktail to ascorbic acid did not enhance urinary pH, [HCHO] or methenamine efficacy. Our data suggest that in Foley catheter patients with chronic asymptomatic bacteriuria secondary to Proteus, Pseudomonas or E. coli infection, the type of urinary pathogen or the urinary pH cannot be used to predict the efficacy of methenamine therapy either with or without urinary acidifying agents.

Aged↗

Electron microscopic demonstration of non-mineralized and hypomineralized areas in dentin and cementum by silver methenamine staining of collagen.

An electron microscopic study on silver methenamine staining of hard dental tissues was made on a material that comprised human permanent teeth and primary tooth germs from human and porcine fetuses. It was demonstrated that silver-stained material consisted of collagen fibrils. In predentin and precementum all collagen fibrils were stained, while collagen fibrils of dentin and cementum were unstained except for some fibrils of minor special areas such as Owen's contour lines, interglobular dentin, Tomes's granular layer, and in cementum small "interglobular-like" areas. It is concluded that silver methenamine visualizes collagen fibrils of hypo- and unmineralized areas in dental hard tissues and therefore may be used to demonstrate abnormal patterns of mineralization. Finally variations of silver methenamine stainability in relation to differences in material and methods were studied and discussed.

Animals↗

Potentiation of the antibacterial effect of methenamine by acetohydroxamic acid.

In vitro testing shows nearly all strains of Proteus to be susceptible to methenamine. However, infection by urease-producing bacteria alkalinizes the urine in vivo and prevents generation of formaldehyde, the active metabolite, from methenamine. We have previously shown acetohydroxamic acid (AHA) to be an effective inhibitor of bacterial urease in vitro and in vivo. We now present data obtained by use of static and dynamic in vitro systems, which show that, by preventing urease-induced alkalinization of urine, AHA enables methenamine to exert its antibacterial effect against representative Proteus species.

Drug Synergism↗

Location of polysaccharide on Chlamydia psittaci by silver-methenamine staining and electron microscopy.

Previous serological studies have indicated that the group antigen of chlamydial organisms is composed of an acidic polysaccharide and a lipid component. The present study was undertaken in an effort to locate this polysaccharide complex by use of electron microscopy and a silver-methenamine marker. The meningopneumonitis strain of Chlamydia psittaci was propagated in HeLa-M cell culture. Organisms were purified by differential centrifugation, treatment with Genetron, and by gel filtration. After fixation and embedding, sections were obtained for electron microscopy. Sections were stained for carbohydrates with silver-methenamine. A double layer of regularly spaced silver grains of uniform size was observed at the periphery of the sectioned organisms tracing the contours of the surface membrane (cell wall). This intensity of staining was observed only when sections were oxidized with periodate prior to silver-methenamine staining. Prior treatment with 1% sodium deoxycholate resulted in a significant reduction in staining. It is considered probable that the periodate-sensitive polysaccharide found at the periphery of the organisms represents, or is a component of, the group antigen of these organisms.

Cell Wall↗

Combined methenamine-silver nitrate and hematoxylin & eosin stain for fungi in tissues.

Initial examination of hematoxylin & eosin-stained tissue from a human brain specimen did not reveal the fungi which were seen in subsequent tissue sections stained with methenamine-silver nitrate. Microabscesses seen in the hematoxylin & eosin-stained sections were not apparent in the methenamine--silver nitrate-stained tissue. Staining with methenamine--silver nitrate and counterstaining with hematoxylin & eosin proved excellent not only for detecting fungus cells, but also for revealing their relationship to the host cellular response in this case and in examples of experimental murine coccidioidomycosis and histoplasmosis.

Animals↗

Cefotaxime for prevention of infectious complications in bacteriuric men undergoing transurethral prostatic resection. A controlled comparison with methenamine.

Forty-two men with urinary tract infection and benign prostatic hyperplasia were randomized into two groups before transurethral resection. One group (22 patients) received Claforan (cefotaxime) peroperatively and thereafter daily for five days. In the other group (20 patients), Hiprex (methenamine hippurate) was given daily from the day before the operation, for a total of six days. All the bacterial isolates were sensitive to cefotaxime. The efficacy of the medication was clinically and bacteriologically evaluated. Postoperative temperature elevation (greater than 38 degrees C) occurred in one of the 22 patients in the cefotaxime group, and in nine of the 20 in the methenamine hippurate group (p less than 0.05). None of the former group, but two patients in the latter, had septicemia. The difference was not statistically significant. The response to treatment was satisfactory in 13 of the 22 patients in the cefotaxime group, but in only one of the 20 treated with methenamine hippurate (p less than 0.005). Antibiotic treatment is recommended for bacteriuric patients undergoing transurethral prostatic resection.

Aged↗