Is methenamine hippurate effective and safe in the prevention of urinary tract infections in adult women compared to placebo or antibiotics?
Näytönastekatsaukset
14.6.2024
Level of evidence: D
Methenamine hippurate may decrease the number of UTIs in adult women with recurrent UTIs compared to placebo (very low evidence). It may be inferior to antibiotics in the prevention of urinary tract infections in adult women with recurrent UTIs. Blinded, large RCTs and long-term safety data are lacking.
| Reference | Study type | Population | Intervention and comparison or exposure | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| «Bakhit M, Krzyzaniak N, Hilder J, et al. Use of methenamine hippurate to prevent urinary tract infections in community adult women: a systematic review and meta-analysis. Br J Gen Pract 2021;71(708):e»1 | Meta-analysis | Adult women (≥ 18 years) with a history of recurrent urinary tract infections (as defined by study authors) Total N=557 included in 6 RCTs (all outcomes), of which 447 were analyzed. n:s varied per outcome | Methenamine hippurate 1g x 2 (dose not reported in one study) compared to placebo or any antibiotic | 1.Symptomatic UTI for 6-12 month follow- up 2.Bacteriuric UTI in 12-month follow-up 3.Number of patients remaining asymptomatic in 6–12-month follow-up | High |
| «Harding C, Mossop H, Homer T, et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority tria»2 | Non-inferiority open-label RCT | Women aged ≥18 years with recurrent UTIs defined as at least three episodes of symptomatic UTI in the previous 12 months or at least two episodes in the past six months. Total N=240 | Methenamine hippurate or antibiotic prophylaxis for 12 months. | Main outcome: Incidence of symptomatic, antibiotic treated UTIs. Secondary outcome: incidence of microbiologically confirmed UTIs. | High |
| «Botros C, Lozo S, Iyer S, et al. Methenamine hippurate compared with trimethoprim for the prevention of recurrent urinary tract infections: a randomized clinical trial. Int Urogynecol J 2022;33(3):571»3 | Open-label RCT | Women over 18 years who had at least two culture-proven UTIs in the prior six months or three in the prior year. Total N=92 | Methenamine hippurate or trimethoprim for 6-12 months. | Urine culture-proven UTI recurrence by 12 months after initiating prophylaxis. | High |
RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis, UTI= urinary tract infection
| Reference | Comments |
|---|---|
| «Bakhit M, Krzyzaniak N, Hilder J, et al. Use of methenamine hippurate to prevent urinary tract infections in community adult women: a systematic review and meta-analysis. Br J Gen Pract 2021;71(708):e»1 | The meta-analysis itself used GRADE methodology and the method was of high quality. However, there were serious risks of bias in all of the six included studies. 5/6 studies were >30 years old and lacked statistical power. The definition of recurrent UTI varied across studies: one study used ≥2 UTIs in the last six months, three studies used ≥3 UTIs in the last 12 months and two studies did not report the inclusion frequency. |
| «Harding C, Mossop H, Homer T, et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority tria»2 | Non-inferiority margin set as one episode of UTI per person year. Patients or researchers were not blinded. Cross-over between groups was relatively common (18% of methenamine group switched to antibiotics). Intention-to-treat analysis was performed. |
| «Botros C, Lozo S, Iyer S, et al. Methenamine hippurate compared with trimethoprim for the prevention of recurrent urinary tract infections: a randomized clinical trial. Int Urogynecol J 2022;33(3):571»3 | Patients or researchers were not blinded. There was variability in follow-up: patients were advised to use methenamine for at least 6 months, and then continue if they wanted. Outcomes were measured at 12 months: some participants had been using methenamine for 12 months, some for 6 months and some 6-12 months. This variability was not accounted for in the analyses (only reported that the mean number of days on medication were similar in both groups). |
Results
Methenamine vs placebo or antiseptic perineal wash in prevention of UTI
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: very low The quality of evidence is downgraded due to study limitations, indirectness (UTI diagnosis based on symptoms only) and very serious imprecision. | |||||
| «Bakhit M, Krzyzaniak N, Hilder J, et al. Use of methenamine hippurate to prevent urinary tract infections in community adult women: a systematic review and meta-analysis. Br J Gen Pract 2021;71(708):e»1 | 2 RCTs, (n=53/31) | 12 months | Not reported | Not reported | RR 0.56 (95% CI 0.13 to 2.35) |
I= intervention; C=comparison; CI=confidence interval, UTI=urine tract infection
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: very low The quality of evidence is downgraded due to study limitations and very serious imprecision (wide CI and small number of patients) | |||||
| «Bakhit M, Krzyzaniak N, Hilder J, et al. Use of methenamine hippurate to prevent urinary tract infections in community adult women: a systematic review and meta-analysis. Br J Gen Pract 2021;71(708):e»1 | 2 RCTs, (n=39/33) | 6-12 months | 15/39 (38.5 %) | 14/33 (42.4 %) | 1.00 (0.27 to 3.66) |
Methenamine vs antibiotics for prevention of UTI
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect or absolute difference (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: low The quality of evidence is downgraded due to study limitations and serious imprecision. | |||||
| «Bakhit M, Krzyzaniak N, Hilder J, et al. Use of methenamine hippurate to prevent urinary tract infections in community adult women: a systematic review and meta-analysis. Br J Gen Pract 2021;71(708):e»1 | 2 RCTs, (n=81/63) | 6-12 months | Not reported | Not reported | Symptomatic UTI RR: 1.95 (0.87 to 4.38) Culture-proven UTI RR: 2.09 (0.72 to 6.09) |
| «Harding C, Mossop H, Homer T, et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority tria»2 | 1 RCT (n=120/120) | 12 months | Symptomatic UTI: 1.38 episodes per person year (95% CI 1.05 to 1.72) Culture-confirmed UTIs 0.53 (0.34 to 0.72) episodes per person-year | Symptomatic UTI 0.89 episodes per person year (95% CI 0.65 to 1.12) Culture-confirmed UTIs 0.41 (0.27 to 0.56) episodes per person-year | Absolute difference: 0.49 episodes more among methenamine users (95% CI 0.08 to 0.90) per person year. Adjusted incidence rate ratio 1.52 (95% CI 1.16 to 1.98) in favor of antibiotics Absolute difference 0.11 (−0.12 to 0.35) |
| «Botros C, Lozo S, Iyer S, et al. Methenamine hippurate compared with trimethoprim for the prevention of recurrent urinary tract infections: a randomized clinical trial. Int Urogynecol J 2022;33(3):571»3 | 1 RCT, (n=43/43) | 6-12 months | ITT analysis: 28/43 (65%) had culture-proven recurrences PP analysis: 30/46 (65%) | ITT analysis: 28/43 (65%) had culture-proven recurrences PP analysis: 26/40 (65%) | No differences between groups (ITT p=1.0, PP p=0.98) |
I= intervention; C=comparison; CI=confidence interval, ITT= intention to treat, PP=per protocol
References
- Bakhit M, Krzyzaniak N, Hilder J, et al. Use of methenamine hippurate to prevent urinary tract infections in community adult women: a systematic review and meta-analysis. Br J Gen Pract 2021;71(708):e528-e537 «PMID: 34001538»PubMed
- Harding C, Mossop H, Homer T, et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial. BMJ 2022;376():e068229 «PMID: 35264408»PubMed
- Botros C, Lozo S, Iyer S, et al. Methenamine hippurate compared with trimethoprim for the prevention of recurrent urinary tract infections: a randomized clinical trial. Int Urogynecol J 2022;33(3):571-580 «PMID: 34115162»PubMed