A Cochrane review [Abstract] 1 included 13 studies with a total of 2 032 subjects. Six trials (654 patients) studied symptomatic UTI and eight trials (796 patients) studied bacteriuria as an outcome measure. 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.
A meta-analysis 2 assessing nitrofurantoin´s efficacy and safety in the prophylaxis of UTI included 26 controlled trials (n=3052) and 16 cohort studies. When compared with no prophylaxis, nitrofurantoin was effective (risk ratio 0.38, 95% CI 0.30 to 0.48). Its prophylactic efficacy was superior to that of methenamine hippurate and comparable to that of other antibacterials (e.g. penicillin, amoxicillin, pivmecillinam, cefaclor, cefixime, trimethoprim/sulfamethoxazole, trimethoprim).
A multicentre, pragmatic, open-label, randomised, non-inferiority trial 3 of 12 months' treatment assessed the clinical effectiveness and cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased in both arms (to 1.38 episodes per person-year; 95% CI 1.05 to 1.72) for methenamine hippurate and 0.89 episodes per person year; 95% CI 0.65 to 1.12 episodes per person-year for antibiotics). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm.
A systematic review and meta-analysis 4included 6 trials (n= 557). 3 compared methenamine hippurate against placebo or control, and 3 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 (RR 0.65, 95% CI 0.40 to 1.07, I²=49%), versus control over 6 or 12 months (RR 0.56, 95% CI 0.13 to 2.35, I²= 93%), and a non-statistically significant trend versus any antibiotic for abacteruria (RR 0.80, 95% CI 0.62 to 1.03, I²=23%). There was a trend towards fewer adverse effects with methenamine hippurate.
Comment: The quality of evidence is downgraded by study quality (inadequate or unclear allocation concealment) and by inconsistency (variability in results across studies).
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