In a controlled trial, co-trimoxazole was more effective than a cranberry extract in reducing the frequency of recurrent urinary tract infections (UTIs) in premenopausal women, however bacterial resistance rapidly reached high levels.

UTIs are common in women, and a significant proportion will suffer recurrent infections. Continuous antibiotic prophylaxis is recommended for those with frequent recurrence, however this leads to high levels of resistant bacteria, both in the causative organisms and in the normal body flora. Evidence suggests that cranberry may be effective in reducing UTI, with several components demonstrating potentially useful effects in vitro and placebo-controlled trials suggesting benefit. The authors of this study aimed to compare a cranberry preparation with a standard antibacterial combination, co-trimoxazole in a non-inferiority trial. Participants were premenopausal women who had at least symptomatic UTI in the year before enrolment. They were randomised to receive co-trimoxazole 480mg at night or a cranberry extract 500mg twice daily, using a double-blind, double-dummy design. Study duration was one year. Primary outcomes were mean number of symptomatic UTI (clinical recurrences [CR]) over 12 months, the proportion of patients with at least 1 symptomatic UTI during 12 months of prophylaxis use, and the median time to the first symptomatic UTI.

Of 753 women assessed for eligibility, 128 were ineligible and 404 did not wish to participate (most commonly because they had a treatment preference), leaving 221 who were randomised (110 to co-trimoxazole, 111 to cranberry). There were 14 (12 and 2) who withdrew consent before receiving any study drug leaving 207 who took at least one dose and were thus eligible for analysis. In this group, there were more clinical recurrences over the 12 month period in the cranberry group than the co-trimoxazole group (4.0 vs. 1.8; P = .02): the difference between the groups (2.2) was greater than the pre-specified non-inferiority margin (1.3 CR). Additionally, the proportion of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (78.2% vs. 71.1%) and the time to first recurrence was shorter (4 vs. 8 months).

Women in the co-trimoxazole group were much more likely to develop resistance: after 1 month, over 80% of Escherichia coli isolates were resistant in the co-trimoxazole group vs. <30% in the cranberry group. In the co-trimoxazole group, resistance to trimethoprim, ampicillin, and ciprofloxacin also increased. After discontinuation, resistance levels returned to baseline after three months.

The authors conclude that in this study, co-trimoxazole was more effective than the cranberry extract used in preventing recurrent UTI in premenopausal women, however this was at the price of high resistance levels. They comment that in practice, many women may prefer to avoid the risk of contracting an infection due to drug-resistant bacteria, and in these women cranberry may be useful despite its lower effectiveness.

In an accompanying Commentary, the author notes that while plant-derived antibacterial compounds may have potent activity in vitro, they often have poor bioavailability due to poor absorption and effective pre-systemic metabolism. As a result, the effective dose of the cranberry extract used may have been too low for efficacy, and quotes alternative work suggesting that higher doses of the active compounds may be effective.