D-Mannose Fails to Prevent Recurrent UTIs

D-mannose did not reduce the proportion of women with recurrent urinary tract infection (UTI), the randomized, placebo-controlled MERIT trial showed.

Over the 6-month study period, 51% of women taking 2-g D-mannose powder daily had a further episode of a suspected UTI for which they contacted ambulatory care compared with 55.7% of women taking a fructose-based placebo powder (P=0.26), reported Gail Hayward, DPhil, of Oxford University in England, and colleagues in JAMA Internal Medicine.

“There had been some small trials of D-mannose previously which showed promise,” Hayward told MedPage Today in an email, but there had never been a study comparing D-mannose to placebo. “I honestly wasn’t sure whether to recommend this to patients as their GP [general practitioner], especially since it is not available on prescription and is quite expensive to buy.”

Based on the results of the trial, “D-mannose should not be recommended by GPs as a way for women presenting to primary care with recurrent UTI to avoid having more episodes,” Hayward added.

D-mannose is a naturally occurring monosaccharide isomer of glucose. Animal studies have shown it may prevent UTIs by inhibiting bacterial adherence to uroepithelial cells, thereby reducing or preventing bacterial colony formation. There has been hope that D-mannose may be an alternative to antibiotic prophylaxis for recurrent UTIs, Hayward and colleagues wrote.

To date, however, evidence for the effectiveness of D-mannose in preventing or treating UTIs has been mixed. A recent systematic review found that there was insufficient evidence to recommend for or against the supplement.

The researchers also looked at a variety of secondary outcomes, none of which demonstrated that D-mannose was superior to placebo. For example, there were no differences between duration of moderately bad or worse participant-reported symptoms on a daily or weekly basis (P>0.99 for both), in the number of microbiologically proven UTIs (P=0.88), or in the number of clinically suspected UTIs (P=0.21) between the two groups.

The number of antibiotic courses prescribed (P=0.29), proportion of women with resistant organisms on culture during acute infection (P=0.59), or hospital admissions related to UTIs (P=0.51) were also similar between the D-mannose group and the placebo group.

Of note, the trial results may have been obscured by the fact that the study did not require laboratory confirmation of UTIs, pointed out Eva Raphael, MD, MPH, and Alison Huang, MD, MAS, both of the University of California San Francisco, in an accompanying editorial. “The trial cannot directly confirm or refute the hypothesis that D-mannose is effective” in reducing symptomatic UTIs based on both presence of symptoms and laboratory confirmation — the gold standard for UTI diagnosis.

Although the American Urological Association recommends confirming a UTI by obtaining urine cultures prior to initiating antibiotic treatment, “multiple professional societies do not encourage routine urine testing for women presenting with typical UTI symptoms suggesting a recurrent episode,” they noted.

“The trial’s negative findings raise an interesting question: even if D-mannose were highly efficacious in preventing UTI recurrence, how much of an effect could it realistically have on either antibiotic overuse or health system burden for UTIs, so long as other aspects of recurrent UTI diagnosis and management remain so problematic?” Raphael and Huang wrote. “What is the greater driver of antibiotic overtreatment for recurrent UTIs in empirical settings — the lack of evidence-based antibiotic-sparing UTI prevention strategies, or the confusion about when and how clinicians should diagnose and initiate treatment if they suspect recurrent UTIs?”

Nevertheless, Raphael and Huang concluded that even if some of the suspected UTI cases were not true episodes of infection, the findings of the MERIT trial indicate that “widespread D-mannose therapy is unlikely to decrease the incidence of patient consultations and clinician visits for suspected recurrent UTIs.”

The double-blind, randomized, placebo-controlled trial was conducted across 99 primary care centers in the U.K. from March 2019 through January 2020. Participants were eligible if they were female, 18 years or older, living in the community, and had evidence of at least two UTIs in the preceding 6 months or three UTIs in the preceding 12 months.

The trial enrolled 598 eligible women with a mean age of 58. Primary outcome data were available for 583 participants — 294 randomized to the D-mannose group and 289 to the placebo group.

Over 6 months of follow-up, participants completed daily diaries that included UTI symptom severity, use of over-the-counter medicines or antibiotics, contacts with healthcare, and use of the EuroQol EQ-5D-5L scale. Participants with mild, continuous UTI-like symptoms completed the diary if they experienced a flare. Participants also completed a weekly questionnaire regarding adherence and symptomatic episodes.

The researchers consulted the primary care records for participants to collect details about participants’ ambulatory visits, results of urine cultures, antibiotic prescriptions, and hospitalizations.

Please enable JavaScript to view the

comments powered by Disqus.