Trimethoprim-sulfamethoxazole (TMP-SMX) is more effective than cranberry extract in preventing recurrent urinary tract infections (rUTI), data from a double-blind noninferiority trial indicate, but antimicrobial resistance remains a major concern.

“The increasing prevalence of isolates of Escherichia coli that are resistant to antimicrobial agents has stimulated interest in novel non-antibiotic methods for the prevention of UTIs,” Mariëlle A. Beerepoot, MD, of the Academic Medical Center in Amsterdam, and colleagues wrote in the Archives of Internal Medicine (2011;171:1270-1278).

Although a previous meta-analysis showed that cranberry supplements reduced UTI recurrences by 39% compared with placebo or no intervention, no studies have assessed how the supplements stack up to standard of care prophylaxis with low-dose TMP-SMX.

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To determine this, the researchers randomly assigned 111 premenopausal women with
rUTIs to receive a 500 mg cranberry supplement twice daily and 110 to receive 480 mg of TMP-SMX once daily.

After 12 months, more patients in the cranberry group experienced at least one symptomatic UTI compared with those in the TMP-SMX group (78.2% vs. 71.1%), with patients in the cranberry group experiencing an average of four clinical recurrences compared with 1.8 in the antibiotic-treated patients, a significant difference between the groups. Patients assigned to receive TMP-SMX also had longer median time to first recurrence than those in the cranberry group (eight vs. four months).

Despite these findings, the researchers advised clinicians that the benefits “should be weighed against the greater development of antibiotic resistance.”

Just one month after treatment initiation, TMP-SMX-resistant E. coli isolates were identified in 86.3% of fecal samples from patients in the antibiotic group vs. 23.7% in the cranberry group, and in 90.5% of asymptomatic bacteriuria isolates from the antibiotic group vs. 28.1% from the cranberry group.

The researchers also observed a simultaneous increase in amoxicillin and fluoroquinolone resistance among patients in the TMP-SMX group.

“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 non-antibiotic prophylaxis,” the researchers wrote. “In those women, cranberry prophylaxis may be a useful alternative despite its lower effectiveness.”

In an accompanying editorial, Bill J. Gurley, PhD, of the Department of Pharmaceutical Sciences at the University of Arkansas in Little Rock, pointed out a potential flaw in the study design. “The comparison may not have been fair in terms of dose and bioavailability of active ingredients,” he wrote.

The amount of the active ingredient A-type proanthocyanidins, a plant polyphenol that blocks the adhesion of E. coli to epithelial cell receptors in the urinary tract, was 9.1 mg/g.

Dr. Gurley pointed out, however, that proanthocyanidins have low oral bioavailability due to “poor water solubility and extensive presystemic metabolism.” Because of these properties, he said that the amount of proanthocyanidins that actually reached the urinary tract in study participants was probably less than 1 mg/day.

TMP-SMX, however, is almost 90% bioavailable, making the ratio of antibiotic to active cranberry ingredient “more like 400:1 instead of 480:500,” Dr. Gurley noted. “Given this discrepancy it is clear why the antibiotic was a more effective UTI preventative than cranberry extract.”

The study findings are not surprising, Dr. Gurley added, as many alternative botanical supplements often perform poorly in clinical trials despite anecdotal benefits and popularity.

Poor performance can be attributed to a lack of established optimum doses for active phytochemicals, Dr. Gurley said. Until more is known about phytochemical disposition in human beings, he observed, “efficacy concerns will continue to plague these products.”

Both he and some of the study researchers agreed that the results of an ongoing dose-finding study might influence the way data from current trial are interpreted.