The authors report no financial relationships relevant to this article.
CASE: Recurrent UTI and antibiotic resistance
A 53-year-old postmenopausal woman with a history of culture-proven recurrent Escherichia coli urinary tract infections (UTIs) presents to the clinic with symptoms of UTI. She was previously treated with a postcoital regimen of trimethoprim/sulfamethoxazole, based on sensitivities identified by culture. A past work-up of her upper and lower urinary tract was negative. You send a catheterized specimen for culture; again, E. coli is identified as the pathogen but proves resistant to her current antibiotic regimen.
What treatment alternatives, aside from antibiotics, are available for this patient—and how might they affect resistance?
Increased antibiotic usage has led to greater bacterial resistance, which is perpetuated by clonal spread. Resistant strains of E. coli have been found in household members, suggesting host-host transmission as a mechanism for dissemination. Alternative treatments that reduce the use of antibiotics may minimize bacterial resistance and increase the efficacy of treatment. In the TABLE , we summarize alternative approaches to the treatment of recurrent UTI. We also describe a strategy to alleviate symptoms.
Alternatives to antibiotics in the treatment and prevention of recurrent UTI
| Category | Type | Examples and doses, if recommended |
|---|---|---|
| Vaginal estrogen | Conjugated estrogen cream Estradiol
| Premarin cream, 0.5–2 g vaginally twice weekly
|
| Nutritive agents | Cranberry juice Cranberry tablets Cystopurin Lactobacilli Blueberry products | Not recommended 1 tablet (300 to 400 mg, depending on manufacturer) twice daily Not recommended Vivag, EcoVag, 1 capsule daily by vagina for 5 days, then once weekly for 10 weeks Not recommended |
| Anti-infective drugs | Methenamine hippurate Methenamine mandelate Methylene blue | Urex or Hiprex, 1 g orally twice daily Mandelamine, 1 g orally 4 times daily Future therapy |
| Urinary acidifiers | Vitamin C/ascorbic acid | 1–3 g orally 3–4 times daily |
| Herbal remedies | Uva ursi Forskolin | Not recommended for long-term use Not recommended |
| Behavioral changes | Adequate hydration Postcoital voiding |
Vaginal estrogen is the only proven alternative to antibiotics for postmenopausal women
A lack of estrogen is a risk factor for UTI and is associated with atrophic mucosa, leading to decreased colonization with lactobacilli, increased vaginal pH, and E. coli colonization.
A randomized, double-blind, placebo-controlled trial of intravaginal estriol cream versus placebo in 93 postmenopausal women found a significant decrease in the rate of UTI among women who used the cream.1 After 8 months of follow-up, the incidence of UTI was 0.5 vs 5.9 episodes per patient-year (P <.001). Interestingly, all pretreatment cultures were negative for lactobacilli. One month after treatment, 61% of women in the estriol group were culture-positive for lactobacilli, compared with 0% of the placebo group.1
A 2008 Cochrane review of nine studies concluded that vaginal estrogen reduces the number of UTIs in postmenopausal women, with variation based on the type of estrogen and duration of use.2
Adverse effects are mild
Twenty-eight percent of the estriol group in the randomized trial described above withdrew from treatment, with 20% citing local side effects, including vaginal irritation, burning, or itching—all of which were mild and self-limited.1 Other possible adverse effects include breast tenderness, vaginal bleeding or spotting, and discharge.2
Clinical recommendations
Given the efficacy of this therapy, we recommend topical estrogen for postmenopausal patients with recurrent UTIs.
Cranberry juice may reduce UTI, but many patients withdraw
from treatment
Cranberries belong to the Vaccinium species, which contains all flavonoids, including anthocyanins and proanthocyanidins. It was previously thought that the acidification of urine produced an antibacterial effect, but several trials have documented no change in urine levels of hippuric acid when cranberry products are given, with no acidification of the urine.3 Current theory suggests that cranberries prevent bacteria from adhering to the uroepithelial cells of the walls of the bladder, by blocking expression of E. coli’s adhesion molecule, P. fimbriae, so that bacteria are unable to penetrate the mucosal surface.4,5 The major benefit of cranberry products over antibiotic prophylaxis is that they do not have the potential for resistance.4
A 2008 Cochrane review concluded that cranberry juice may reduce symptomatic UTIs, particularly among young, sexually active women—but there is a high rate of withdrawal from treatment.6 The optimal method of administration and dose remain unclear. In contrast, two recent randomized, controlled trials—published after the Cochrane review—found no difference in the rate of recurrent UTI in premenopausal women.7,8 Adverse effects in these two trials included constipation, heartburn, loose stools, vaginal itching and dryness, and migraines. Of note, there was no statistical difference in side effects between the cranberry and placebo groups.7