Vaccines for the prevention of recurrent urinary tract infections: a systematic review

Objectives To systematically review the evidence regarding the efficacy of vaccines or immunostimulants in reducing the recurrence rate of urinary tract infections (UTIs). Materials and Methods The Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), PubMed, Cochrane Library, World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal, and conference abstracts were searched up to January 2018 for English-titled citations. Randomised placebo-controlled trials evaluating UTI recurrence rates in adult patients with recurrent UTIs treated with a vaccine were selected by two independent reviewers according to the Population, Interventions, Comparators, and Outcomes (PICO) criteria. Differences in recurrence rates in study populations for individual trials were calculated and pooled, and risk ratios (RRs) using random effects models were calculated. Risk of bias was assessed using the Cochrane Collaboration's tool and heterogeneity was assessed using chi-squared and I-2 testing. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of evidence (QOE) and summarise findings. Results In all, 599 records were identified, of which 10 studies were included. A total of 1537 patients were recruited and analysed, on whom data were presented. Three candidate vaccines were studied: Uro-VaxomA (R) (OM Pharma, Myerlin, Switzerland), UrovacA (R) (Solco Basel Ltd, Basel, Switzerland), and ExPEC4V (GlycoVaxyn AG, Schlieren, Switzerland). At trial endpoint, the use of vaccines appeared to reduce UTI recurrence compared to placebo (RR 0.74, 95% confidence interval [CI] 0.67-0.81; low QOE). Uro-Vaxom showed the greatest reduction in UTI recurrence rate; the maximal effect was seen at 3 months compared with 6 months after initial treatment (RR 0.67, 95% CI 0.57-0.78; and RR 0.78, 95% CI 0.69-0.88, respectively; low QOE). Urovac may also reduce risk of UTI recurrence (RR 0.75, 95% CI 0.63-0.89; low QOE). ExPEC4V does not appear to reduce UTI recurrence compared to placebo at study endpoint (RR 0.82, 95% CI 0.62-1.10; low QOE). Substantial heterogeneity was observed across the included studies (chi-squared = 54.58; P < 0.001, I-2 = 84%). Conclusions While there is evidence for the efficacy of vaccines in patients with recurrent UTIs, significant heterogeneity amongst these studies renders interpretation and recommendation for routine clinical use difficult at present. Further randomised trials using consistent definitions and endpoints are needed to study the long-term efficacy and safety of vaccines for infection prevention in patients with recurrent UTIs.