| Reference | Study type | Population | Intervention and comparison or exposure | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| «Bakhit M, Krzyzaniak N, Hilder J, et al. Use of me...»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 t...»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 hippu...»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 me...»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 t...»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 hippu...»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 me...»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 me...»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 me...»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 t...»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 hippu...»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