Novel and Emerging Treatments
Topical Estrogen for Recurring UTI
Low estrogen levels thin the walls of the vagina, increasing a woman’s risk of developing UTIs (University of Maryland Medical Center 2011). As a result, topical estrogen may represent a treatment option in some cases of UTI among women.
Two different methods of administering topical estrogen have been effective at reducing the frequency of recurring UTIs in postmenopausal women. These include an estradiol-releasing ring and intravaginal estriol cream (Raz 1993; Eriksen 1999; Krause 2009). Estradiol-releasing rings may also acidify the urine, which may help combat intravaginal bacterial growth. As of late 2012, a Phase 4 clinical trial is examining the efficacy of intravaginal estrogen and lactobacilli for preventing recurrent UTIs (ClinicalTrials.gov 2009).
One of the most important early steps for bacteria to infect the urinary tract is their adhesion to the outside of the cells that line the urinary tract. Bacteria use small finger-like projections, called fimbriae, to bind to the urinary tract lining. Fimbriae are coated with proteins, called lectins, which mediate this process (Klemm 2010). Researchers have discovered that one of these lectins, known as FimH, is crucial for this process; they have therefore developed medications that inhibit the activity of FimH (Jiang 2012; Klein 2010).
To make even better therapies, scientists have developed many different compounds that can inhibit FimH and are continuously tweaking the molecules to improve their effectiveness. The most promising compounds have a similar core structure and are called alpha-D-mannosides. Although these drugs have not yet been tested in humans, studies have found that these chemicals can significantly reduce the amount of bacteria that colonize the bladder in animal models of UTI (Jiang 2012; Klein 2010). In some studies, the FimH blockers drastically reduce the amount of bacteria in the bladder by approximately as much as standard antibiotic treatments (Jiang 2012). These FimH blockers have also been effective in animal models of catheter-associated UTIs (Guiton 2012).
Hyaluronic Acid and Chondroitin Sulfate Injections
Another emerging treatment focuses on the bladder wall. The cells that line the inside of the bladder, known as urothelial cells, are an important part of the body’s defense against UTIs (Bassi 2012; Khandelwal 2009). These cells help to keep undesirable substances (eg, bacteria) from penetrating into the deeper layers of the bladder and also make substances, known as proteoglycans, which form a layer of glycosaminoglycans (GAGs) on the inner surface of the bladder. Any damage to the GAG layer facilitates the adhesion of bacteria to the bladder wall and may play a role in recurrent UTIs (Damiano 2011; Bassi 2012).
New treatments that focus on restoring the integrity of the GAG wall are being developed for preventing recurrent UTIs. These treatments involve injecting some of the substances used to construct GAG, such as hyaluronic acid and chondroitin sulfate, directly into the bladder. This process is also known as intravesical administration. Intravesical administration of hyaluronic acid and chondroitin sulfate has been shown to reduce the number of UTIs in women with recurrent UTIs (Constantinides 2004; Damiano 2011; Bassi 2012; DeVita 2012). Mild bladder irritation has been reported as a side effect of this treatment in some patients (Constantinides 2004; Bassi 2012). Although this treatment is available in Canada and Europe, it has not been approved by the Food and Drug Administration (FDA) for use in patients because of limited clinical trial data.