Significance of Non-Antimicrobial Prevention of Urinary Tract Infection among Women: Future Perspective

Abstract

Urinary tract infection (UTI) is a very common disease among women. It has been estimated that about 50 to 60.0% of women will get at least one urinary tract infection in their lifetime 1 . In uncomplicated UTI the infection is not associated with structural or functional disorders of the urinary tract. After this uncomplicated UTI around 25% of women experience a recurrent infection within 6 to 12 months, and around 5.0% have several episodes within a year 2 . Recurrent UTIs are mostly occurred in young women; however, postmenopausal women are also often affected 3 . It has been found that about 75 to 85% of uncomplicated UTIs are caused by Escherichia coli 4 . According to the classic understanding of pathogenesis, almost all recurrent UTIs are ascending re-infections by the same clone or a different clone from the rectal reservoir 5 . However, an alternative pathway has emerged. In murine cystitis, uropathogenic E coli binds to, invades, and replicate within the bladder urothelium to form intracellular bacterial communities, which dissociate and ultimately establish intracellular reservoirs that can seed recurrent UTIs 6 . The presence of exfoliated intracellular bacterial communities and filamentous bacteria in the urine of women with acute cystitis suggests that the same intracellular bacterial community pathogenic pathway could have a role in human beings. These findings support the occurrence of an intracellular bacterial niche in some women with cystitis that could have important implications for recurrence and treatment of UTIs 7 . According to international guidelines, prevention of recurrent UTIs includes counselling and behavioural modifications followed by non-antimicrobial measures; antimicrobial prophylaxis is indicated only when nonantimicrobial measures are ineffective 5 .For the prevention of UTI many non-antimicrobial measures have been tested like local hormonal support in postmenopausal women, cranberry products, probiotics, immunoactive prophylaxis, dmannose, endovesical instillation of hyaluronic acid and chondroitin sulphate 8. Evidence for most of these interventions is low or supported only by results from small prospective randomised clinical trials. Immunoprophylaxis with UroVaxom is the only intervention that has grade B recommendation because it was more efficacious than placebo in several randomised placebo-controlled trials 8 . Although UroVaxom is made from an extract of heat-killed uropathogenic E. coli and thus can stimulate an improved immune response at infected sites, such as the urinary tract, it cannot be considered a vaccine against infections exclusively caused by uropathogenic E coli. Development of a specific vaccine against extra-intestinal pathogenic E coli, including uropathogenic E coli, would offer another non-antimicrobial option for prevention of recurrent UTIs, which could provide a great clinical advantage.Huttner et al 9 have tested a bioconjugate vaccine containing the O-antigens of four E coli serotypes. This tetravalent vaccine candidate was well tolerated...