Cranberry capsules are less effective than prophylactic trimethoprim-sulfamethoxazole at preventing recurrent urinary tract infections in premenopausal women, according to a report in the July 25 issue of Archives of Internal Medicine.
However, the emergence of resistance to amoxicillin and the quinolones as well as to trimethoprim-sulfamethoxazole (TMP-SMX) was very rapid and affected approximately 90% of the women who took the antibiotic, compared with only 28% of those who took cranberry capsules. This adverse outcome must be balanced against the antibiotic’s greater effectiveness, said Dr. Marielle A. J. Beerepoot of the Academic Medical Center, Amsterdam, and her associates.
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In this study, resistance to amoxicillin and the quinolones as well as to trimethoprim-sulfamethoxazole (TMP-SMX) affected approximately 90% of the women who took the antibiotic, compared with only 28% of those who took cranberry capsules.
"From clinical practice and during the recruitment phase of this study, we learned that many women are afraid of contracting drug-resistant bacteria using long-term antibiotic prophylaxis, and preferred either no or nonantibiotic prophylaxis. In those women, cranberry prophylaxis may be a useful alternative despite its lower effectiveness," they noted (Arch. Intern. Med. 2011;171:1270-8).
The investigators performed a randomized double-blind noninferiority trial to directly compare 1 year of prophylaxis with TMP-SMX (one 480-mg tablet once daily) against a capsule containing 500 mg cranberry extract (one capsule twice daily) for preventing recurrent UTI in 221 premenopausal women who had at least three UTIs during the previous year. The study subjects were treated at 10 medical centers across the Netherlands during a 2-year period and followed for 15 months, or 3 months after they stopped taking prophylaxis.
After 1 year of treatment, the mean number of clinical recurrences of UTI was 1.8 for TMP-SMX, compared with 4.0 for cranberry capsules. This difference exceeded the limit for noninferiority.
The proportion of women who developed at least one symptomatic UTI while on prophylaxis was 71.1% with TMP-SMX, compared with 78.2% with cranberry capsules. The median time to first recurrence was 8 months with TMP-SMX, compared with 4 months with cranberry capsules.
The median number of antibiotic prescriptions for UTI from the subjects’ primary care physicians during the study period was twice as high in the cranberry group (1) as in the TMP-SMX group (0.5). Nitrofurantoin was the drug most often prescribed for both groups, followed by norfloxacin.
Within 1 month of beginning antibiotic prophylaxis, the rate of resistance to TMP-SMX, TMP alone, and amoxicillin in samples of both urine and feces soared from 21%-28% to 73%-91%. Resistance rates returned to baseline within 3 months of discontinuing antibiotic prophylaxis.
The two interventions were equally well tolerated. "There were no statistically significant differences between the TMP-SMX and the cranberry groups in the percentages of patients with any or a specific adverse event or serious adverse event. In the TMP-SMX group, one woman had a serious adverse event (Stevens-Johnson syndrome) [that] led to her withdrawal [from the study]. There were no serious adverse events in the cranberry group," Dr. Beerepoot and her colleagues said.
This study was limited in that the dropout rate was quite high: only 54 of 110 women in the TMP-SMX group (49%) and only 45 of 111 women in the cranberry group (41%) completed the final assessment. However, these rates are in keeping with those of previous UTI trials with much shorter follow-up periods of 6 months or less, the investigators said.
The trial also was hampered by the fact that the optimal dosage of cranberry extract is still not known. A dose-finding study is now under way. In this study, the daily dose was equivalent to that in 75 mL of commercially available cranberry juice containing 27% cranberry, they noted.
This study was supported by the Netherlands Organisation for Health Research and Development. The cranberry and placebo capsules were provided by Springfield Nutraceuticals BV. Dr. Beerepoot reported no relevant financial disclosures.