With increasing concerns over the rise of antibiotic resistance, there has been great interest in developing non-antibiotic prophylactic strategies for recurrent urinary tract infections (RUTIs). There has been a rise in the number of randomised controlled trials (RCTs) evaluating the clinical efficacy and safety of both new and existing vaccines for UTI prophylaxis in recent years. The aim of this systematic review was to evaluate all available evidence from RCTs on the effectiveness, tolerability and safety of vaccines for the prophylaxis of recurrent uncomplicated UTIs in adults.

We carried out a systematic literature search in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines in the CENTRAL (Cochrane Central Register of Controlled Trials), EMBASE and MEDLINE (PubMed®) databases from inception to 21st October 2017. 

For the construction of the search strategy, the following descriptors and their respective synonyms were used: urinary tract infection, vaccination and the names of vaccines currently in use (Uro-Vaxom®, Uromune®, and Solco-Urovac®). Abstracts from conferences or clinical trial registries were not considered. No publication year restrictions were enforced. Only articles in the English language were included in the analysis.

Two independent reviewers searched for and included randomized controlled trials that compared the prevention of uncomplicated UTIs in adult patients (≥18yrs) using vaccines/immunostimulants (intervention group) with placebo or non-placebo controls (control group). Data extraction and quality assessment was performed independently by two reviewers using a pre-designed data extraction form.

The primary outcome measure was the mean frequency of UTI recurrences. Adverse events (AEs) were assessed as a secondary outcome. Risk of bias was performed using the Jadad scale. Due to heterogeneity in the outcome reporting between studies, a narrative review of the results for each study was performed.

We identified 3153 records and included nine RCTs that met the eligibility criteria. Of these, five studied Uro-Vaxom®/OM-89 (sample size 955, median Jadad score 3) three studied Solco-Urovac® (sample size 220, median Jadad score 2) and one studied ExPEC4V (sample size 194, Jadad score 4). 

All studies evaluating Uro-Vaxom®/OM-89 demonstrated a significant reduction in the incidence of UTIs when compared with placebo. The largest study to date evaluating the medium-term therapeutic efficacy of Uro-Vaxom® over a 12-month follow-up demonstrated the mean rate of recurrence to be significantly lower in the treatment group than in the placebo group (0.84 vs. 1.28; p=0.0026) (1).

Solco-Urovac® was also able to significantly reduce UTI recurrence and prolonged the time to re-infection. However, in one study this was only achieved after a booster cycle of the vaccine was administered to the patients a few months after the primary immunisation (2).

Interestingly, no significant reductions were observed in the mean number of UTIs caused by vaccine-specific serotypes in ExPEC4V-treated patients when compared with placebo. However, significantly fewer UTIs caused by E. coli of any serotype were reported in the treatment group compared with placebo (0.414 mean recurrences vs 0.610 mean recurrences per patient respectively; p=0.038) (3).

All three immunostimulants had a good safety profile with no severe treatment-related AEs being reported.

The current evidence suggests that there is therapeutic benefit in the use of Uro-Vaxom®, Solco-Urovac® and ExPEC4V as safe prophylactic agents against RUTIs in adult patients. However, the studies were heterogeneous with short-term follow-up periods.

The findings of this systematic review were limited by the lack of high quality RCTs, inconsistent definitions of UTI, heterogeneous measures of outcome between studies, the limited number of studies evaluating each vaccine and the exclusion of potentially relevant studies due to the search criteria and methodology employed.

The therapeutic benefits of vaccines for uncomplicated UTI prophylaxis seem promising but larger-scale, longer-term and higher-quality trials that use uniform outcomes and definitions are warranted to better compare alternatives and draw conclusions in future.

Bauer H.W., Alloussi S., Egger G., Blumlein H.M., Cozma G., Schulman CC. A long-term, multicenter, double-blind study of an Echerichia coli extract (OM-89) in female patients with recurrent urinary tract infections. Eur Urol 2005 April 2005;47(4):542-548.
Uehling D.T., Hopkins W.J., Elkahwaji J.E., Schmidt D.M., Leverson GE. Phase 2 clinical trial of a vaginal mucosal vaccine for urinary tract infections. J Urol 2003 01 Sep 2003;170(3):867-869.
Huttner A, Hatz C, Dobbelsteen G, Abbanat D, Hornacek A, Frolich R, et al. Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial. Lancet infectious diseases 2017;(no pagination).