Hypothesis / aims of study
Urinary tract infections (UTIs) are among the most common bacterial infection and resistance to antibiotics is on the rise. This review aims to assess the literature on non-antibiotic prophylaxis for recurrent UTI, focussing on less recognised strategies, namely vaccination and intravesical therapy.
Study design, materials and methods
Embase, Pubmed and the Cochrane Library were searched from January 2000 to August 2018 for articles on non-antibiotic prophylaxis for recurrent UTIs published in English language. The search was limited to human studies comprising adult subjects (>18 years) with no past medical history of significant urinary tract or renal disease (such as renal transplantation, spinal cord injury, neurogenic bladder, chronic bladder pain syndrome or overactive bladder). Studies investigating pregnant women or those concerning complex or perioperative UTI were excluded. Results were analysed according to the Oxford Centre for Evidence-based Medicine (OCEBM) Levels of Evidence March 2011.
Database searching revealed 4109 studies and 124 abstracts were reviewed. There is compelling evidence of the efficacy of intravesical Hyaluronic Acid with or without chondroitin Sulphate. Hyaluronic acid and chondroitin sulphate intravesical instillation is believed to repair the damaged GAG layer, preventing bacterial infection. HA also blocks the intercellular adhesion molecule-1 (ICAM-1) receptor, preventing leukocyte activation thereby reducing inflammation. Pooled analysis from a meta analysis analysis revealed a significantly reduced UTI rate per patient-year (MD 3.41, 95 % CI −4.33 to −2.49). Subgroup analysis of the two RCTs supported this finding (MD 2.45, 95 % CI −4.63 to −0.28). A major limitation of this meta-analysis is the small number of trials and low participant number in each. Evidence rated level 1a-.
Evidence for intravesical heparin is more limited with an OECBM level 4. Heparin sulphate is a GAG present in the bladder urothelial lining and heparin instillation is thought to aid the repair this GAG lining and prevent recurrent infection. Studies investigating its effects are limited by significant methodological flaws including small sample sizes and limited follow up.
A number of oral and vaginal vaccines containing bacterial extracts are being tested for the prevention of refractory UTI. These include OM-89 (Uro-Vaxom), Urovac and Uromune. OM-89 is an oral immunostimulant containing 18 species of heat-treated uropathogenic E coli. Four meta-analyses have been published investigating the effect of OM-89 which suggest OM-89 is a highly effective vaccine. However, there is no reported data on the long-term efficacy and many of the included studies had unclear methodology; evidence level 1a-. Urovac is a vaginal suppository containing 10 heat-treated bacterial species including 6 serotypes of E. coli; evidence an OCEBM level 1a. Uromune is a sublingual spray containing the inactivated bacteria; evidence supporting its use is rated level 3.
Interpretation of results
This systematic review has highlighted some of the key antibiotics treatments currently available for the management of recurrent urinary tract infections. Formal evidence of the more historic treatments is more lacking in comparison to the newer vaccines that have been developed. However these treatments are supported by the far greater depth of experience on their use and safety. For many urologists they offer a safe and relatively efficacious alternative to prophylactic antibiotics for patients willing to undergo regular intravesival instillation. In contrast the UTI vaccines, aiming to galvanise the patient’s own immune system into fighting early UTI offers an exciting new management approach. There is strong early evidence to support their effectiveness however in all cases results must be considered in the context of limited follow up. Yet strong early efficacy and safety data warrants their discussion with patients as manaements options.