New approach eyed for recurrent UTIs

One woman in five develops a urinary tract infection (UTI) during her lifetime, according to the National Institute of Diabetes and Digestive and Kidney Diseases.¹ About one-third of women develop frequent recurrent episodes, which can call for repeated rounds of antimicrobial treatment.²

Science is now eyeing the use of probiotics in UTI treatment.³ A depletion of vaginal lactobacilli has been associated with urinary tract infection risk. Scientists have theorized that replenishing these bacteria might be beneficial. Researchers conducted a double-blind placebo-controlled trial to investigate this theory, with positive results indicated for use of a Lactobacillus crispatus intravaginal suppository now under development.

"The next step for us is a larger study, pure and simple," says the paper's lead author, Ann Stapleton, MD, FACP, professor in the Division of Allergy & Infectious Diseases at the University of Washington School of Medicine in Seattle. "We would like to confirm our data in a larger group of women."

To perform the study, researchers enrolled women ages 18-40 with current, symptomatic, uncomplicated cystitis and a history of recurrent urinary tract infections. The women were randomized to receive a Lactobacillus crispatus intravaginal suppository probiotic (Lactin-V, under development by Osel, Mountain View, CA) or a placebo for five days, then once a week for 10 weeks.

Findings indicate the probiotic intravaginal suppository might reduce the rate of recurrent UTI in UTI-prone women by about one-half. Researchers report that among the 50 women who received Lactin-V, the rate of culture-confirmed UTI was 15%, as compared with 27% among women who received placebo (relative risk [RR] 0.5; 95% confidence interval [CI] .2–1.2). Women who used the suppository who achieved a high-level L. crispatus vaginal colonization pattern had a significant reduction in recurrent episodes compared with those who didn't. Women who used the placebo drug didn't experience such a reduction, regardless of their pattern of colonization.

What is the next step?

While the current study did not compare Lactin-V to prophylactic antibiotics, a 2008 meta-analysis of 10 randomized controlled trials that looked at continuous antimicrobial prophylaxis found rates of recurrent UTI reduced to 12% (24 of 195 participants) compared with 65% (116 of 177 participants) among placebo recipients. The 2008 meta-analysis showed a relative risk of recurrent UTI (RR, 0.21; 95% CI, 0.13-0.33) that is comparable to the findings of the current probiotic study.

Lactin-V is being developed as an investigational new drug for prescription use for specific medical indications in women's health, says Peter Lee, MD, founder of Osel and associate professor of medicine in the Department of Medicine at Stanford University. The primary focus of the probiotic's research is on recurrent urinary tract infections; however, investigators also are looking at its potential use against bacterial vaginosis, says Lee.

Osel plans to undertake a Phase III multi-center trial, says Lee. The company is seeking funding for the research, he says.

Recurrence what to do?

For women who have three or more recurrences in a year, urologic evaluation is indicated to rule out pelvic and gynecologic abnormalities. Radiographic and cystoscopic evaluation can check for anatomical abnormalities. Postmenopausal women also should be evaluated for renal function and emptying.

When abnormalities are ruled out, providers can choose from several therapeutic options for recurrent infections.⁴ Chronic low-dose antibiotic symptomatic treatment with the antibiotics nitrofurantoin or trimethoprim-sulfamethoxazole can be used. Either of these drugs can be used for 6-12 months, followed by an antibiotic-free period and a re-evaluation for return of infection.5

Drinking cranberry juice might prevent Escherichia coli, Staphylococcus aureus, and other UTI-causing bacteria from adhering to the urinary tract and forming biofilms in it, according to a 2010 study.6 Researchers had study participants drink water or cranberry juice cocktail, then they studied the effects of their urine on bacteria. Scientists used an atomic force microscope probe to measure the bacteria's ability to adhere, which is the beginning step necessary for the biofilm formation seen in UTIs.

Researchers report urine from volunteers who drank cranberry juice cocktail prevented bacterial adhesion and biofilm formation. Bacteria treated with urine from volunteers who drank water were able to stick to the probe and form biofilms.6

References

National Institute of Diabetes and Digestive and Kidney Diseases. Urinary tract infections in adults. Fact sheet. Accessed at http://kidney.niddk.nih.gov/kudiseases/pubs/utiadult.
Ikaheimo R, Siitonen A, Heiskanen T, et al. Recurrence of urinary tract infection in a primary care setting: analysis of a 1-year follow-up of 179 women. Clin Infect Dis 1996; 22:91-99.
Stapleton AE, Au-Yeung M, Hooton TM, et al. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis 2011; 52:1,212-1,217.
Sen A. Recurrent cystitis in non-pregnant women. Clin Evid (Online) 2008. Pii:0801.
Duplessis C, Warkentien T, Bavaro M. Uropathogenic Escherichia coli. Fem Patient 2011; 36:18-23.
Tao Y, Pinzon PA, Camesano TA. Cranberry juice's inhibitive effects on uropathogenic bacteria adhesion. Presented at the 239th American Chemical Society National Meeting & Exposition. San Francisco; March 2010.