Introduction

The risk of urinary tract infection (UTI) recurrence is significant after one infection and is defined as 2 urine-culture positive UTIs within 6 months or 3 within 1 year with associated symptoms. Depending on the menopausal symptoms, the primary treatment includes antibiotic prophylaxis and vaginal estrogen for prevention of recurrent UTIs. However, long-term use of antibiotics can cause adverse effects and microbial resistance. Methenamine hippurate, a bacteriostatic agent, has been effective in the prevention of recurrent UTIs in small populations, followed up for about 6 months to 1 year. There is lack of data on the long-term use of methenamine hippurate.

Aim

To evaluate methenamine hippurate as an alternative treatment to a low-dose antibiotic for the prevention of recurrent UTIs and to compare the recurrence rates within 1 year with trimethoprim.

Method

Study Design

• Non-blinded, randomized study  

Patient Profile

• Women aged 18-99 years with confirmed diagnosis of recurrent UTI
• In addition to a documented urine-positive culture, they have had symptoms including acute dysuria, suprapubic pain, fever, worsening urinary urgency, frequency and urinary incontinence
• Women who received antibiotic prophylaxis for recurrent UTI but had not taken it for a minimum of 30 days

Treatment Strategy

• A total of 92 women were randomized to receive daily prophylaxis with methenamine hippurate or trimethoprim for a minimum duration of 6 months
• Both intent-to-treat and per-protocol analyses were performed if patients received the alternative drug after randomization or experienced adverse reactions
• Multivariate models were used to assess the likelihood of recurrence

Endpoints

Primary Endpoint

• Recurrent UTI at 1 year

Secondary Endpoints

• Time to subsequent infection in days
• Number or UTI recurrences at 1 year

Safety Endpoint

• Adverse events (AEs)

Results

• Baseline characteristics of cohort were as follows
  • Mean age 71.9+3 years
  • Mean BMI of 29.5+9 kg/m2
  • 4% were menopausal
  • 7% were on concurrent vaginal estrogen cream
• The final analysis included 86 women
• There were no differences in recurrent UTI in the intent-to-treat (ITT) and per-protocol (PP) set as seen in Figure 1.

 

Figure 1. Recurrent UTI at 1 year

• The time to subsequent infection and number of UTI recurrence at 1 year was comparable between the groups as seen in Table 1

Table 1. Comparison of secondary outcomes

	Methenamine hippurate	Trimethoprim	P value
Time to subsequent infection (ITT) in days	119.3+94.1	100.7+84.4	0.52
Time to subsequent infection (PP) in days	113.0+93.9	106.5+84.9	0.88
Number of UTI recurrences at 1 year (ITT)	1.6+1.9	1.5+1.7	0.72
Number of UTI recurrences at 1 year (PP)	1.4+1.5	1.8+2.1	0.36

• Risk factors like age, number of UTI episodes in the previous year, menopausal status, duration of treatment prophylaxis and use of estrogen vaginal cream did not significantly affect the UTI recurrence rates or number of subsequent infections in both groups
• AEs was reported by 10.9% in the overall cohort
• Diarrhoea was the most common AE reported by 1 and 2 patients in trimethoprim and methenamine hippurate groups respectively

Conclusion

• Methenamine hippurate may be an acceptable alternative to trimethoprim for the prevention of recurrent urinary tract infection (UTI) in women
• The rate of UTI recurrence and adverse effects with methenamine hippurate was comparable to trimethoprim

Int Urogynecol J. 2022 Mar;33(3):571-580. Doi: 10.1007/s00192-021-04849-0.