title: Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic review and meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  Increasing antimicrobial resistance has stimulated interest in nonantibiotic prophylaxis of recurrent urinary tract infections. We assessed the effectiveness, tolerability and safety of nonantibiotic prophylaxis in adults with recurrent urinary tract infections.
  
  
  METHODS
  MEDLINE®, EMBASE™, the Cochrane Library and reference lists of relevant reviews were searched to April 2013 for relevant English language citations. Two reviewers selected randomized controlled trials that met the predefined criteria for population, interventions and outcomes. The difference in the proportions of patients with at least 1 urinary tract infection was calculated for individual studies, and pooled risk ratios were calculated using random and fixed effects models. Adverse event rates were also extracted. The Jadad score was used to assess risk of bias (0 to 2-high risk and 3 to 5-low risk).
  
  
  RESULTS
  We identified 5,413 records and included 17 studies with data for 2,165 patients. The oral immunostimulant OM-89 decreased the rate of urinary tract infection recurrence (4 trials, sample size 891, median Jadad score 3, RR 0.61, 95% CI 0.48-0.78) and had a good safety profile. The vaginal vaccine Urovac® slightly reduced urinary tract infection recurrence (3 trials, sample size 220, Jadad score 3, RR 0.81, 95% CI 0.68-0.96) and primary immunization followed by booster immunization increased the time to reinfection. Vaginal estrogens showed a trend toward preventing urinary tract infection recurrence (2 trials, sample size 201, Jadad score 2.5, RR 0.42, 95% CI 0.16-1.10) but vaginal irritation occurred in 6% to 20% of women. Cranberries decreased urinary tract infection recurrence (2 trials, sample size 250, Jadad score 4, RR 0.53, 95% CI 0.33-0.83) as did acupuncture (2 open label trials, sample size 165, Jadad score 2, RR 0.48, 95% CI 0.29-0.79). Oral estrogens and lactobacilli prophylaxis did not decrease the rate of urinary tract infection recurrence.
  
  
  CONCLUSIONS
  The evidence of the effectiveness of the oral immunostimulant OM-89 is promising. Although sometimes statistically significant, pooled findings for the other interventions should be considered tentative until corroborated by more research. Large head-to-head trials should be performed to optimally inform clinical decision making.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: M.A.Beerepoot@amc.uva.nl.
authors.forename: M A J
authors.initials: MA
authors.lastname: Beerepoot
authors.forename: S E
authors.initials: SE
authors.lastname: Geerlings
authors.forename: E P
authors.initials: EP
authors.lastname: van Haarst
authors.forename: N Mensing
authors.initials: NM
authors.lastname: van Charante
authors.forename: G
authors.initials: G
authors.lastname: ter Riet
mesh_terms: D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D014552:Urinary Tract Infections / Q000517:prevention & control*
keywords: RCT; UTI; meta-analysis; prevention and control; rUTI; randomized controlled trial; recurrent urinary tract infection; review; urinary tract infection; urinary tract infections