**4. Discussion**

for short-term use of urinary catheters but not for long-term use (Trautner &Darouiche, 2004). Several other substances were reported to inhibit development of bacterial bio-film formation including type A proanthocyanidins, hesperidin, apigenin,naringin and rhoifoli‐

One important survival mechanism of UPEC is the creation of an intracellular reservoir. Within the epithelial cell, the UPEC are able to resist antibiotic treatment by binding to Rab 27 b/CD 63 positive vesicles. Forskolin, the active component of the Coleus forskohlii, has been proven to increase the content of cyclical adenosine monophosphate (cAMP) in urothe‐ lial cells, leading uropathogenic bacteria to exit the urothelial cells. It was shown that cAMP levels regulate the exocytosis of these vesicles depending on the bladder distension. These findings could lead to new approaches for the treatment and prevention of recurrent urinary

Hormonal deficiency in postmenopausal women results in thinning of the vaginal and ure‐ thral mucosa and more importantly to disruption of the normal vaginal flora and therefore to an increased risk for UTIs (Head, 2008). Several studies could demonstrate, that replacing

In a randomized study postmenopausal women received either intra-vaginally administered estradiol or placebo. At the end of the study a significant reduction in the incidence of UTIs in the treatment group compared to the placebo group was noted. Of interest is also the ob‐ servation that Lactobacilli that were absent in the vaginal cultures of patients of the treat‐

Darouiche et al. conducted a prospective, randomized, placebo-controlled, double-blind pi‐ lot trial to examine the efficacy of bacterial interference in preventing urinary tract infection (Darouiche et al., 2005). In this study 27 patients with spinal cord injury were included. Pa‐ tients were randomly assigned either to have their bladders inoculated with either E. coli 83972 (experimental group) or sterile normal saline (control group). Patients whose bladders became colonized with E. coli 83972 were half as likely (P=.01) than non-colonized patients

Billips et al. demonstrated recently that deletion of the O antigen ligase gene, waaL, from the uropathogenic E. coli isolate NU14 results in a strain that stimulates enhanced urothelial cy‐ tokine secretion (Billips et al., 2009). They could show that NU14 DwaaL stimulated an en‐ hanced interleukin-6 secretion by mouse macrophages, compared with secretion by the wild type. Of great importance is the fact that mice vaccinated via instillation into the bladder de‐ veloped protective responses that prevented persistent colonization after bladder challenge with NU14, yet NU14 DwaaL failed to persistently colonize the mouse bladder. They could

ment group at the beginning of the trial reappeared in 61% (Raz &Stamm, 1993).

na, and others. None of these substances made it into clinical trials so far.

tract infections (Bishop et al., 2007, Gonzalez-Chamorro et al.).

estrogene in this patient population can reduce the incidence of UTIs.

**3.8. Instillation of attenuated bacteria into the urinary bladder**

to develop UTI during the subsequent year.

**3.6. Stimulation of cyclic adenosine/forskolin**

168 Recent Advances in the Field of Urinary Tract Infections

**3.7. Hormone therapy**

Immune-based treatment strategies for patients with recurrent UTIs are of special interest. Several promising new approaches including bladder colonization with attenuated bacteria and intravesical vaccination were published recently and discussed in this chapter. Further‐ more, studies suggest that the use of inhibitors of bacterial adherence to urothelial cell and inhibitors of biofilm formation receptors hold great promise. Moreover, stimulators of cyclic AMP inside urothelial cells and the recent advancements in the development of vaccines are an interesting initiative in this field. For some of the plant –based prevention and treatment strategies only little scientific evidence for the prevention and treatment of urinary tract in‐ fection exist.
