A novel therapeutic approach to treat life-threatening recurrent urinary tract infections in postmenopausal women

PROJECT SUMMARY Poor management of recurrent urinary tract infections (rUTIs) in women can lead to severe and potentially life-threatening complications such as septicemia, septic shock, renal failure, and even mortality. Post- menopausal women are particularly vulnerable to rUTIs due to decreased estrogen levels, which promotes changes in vaginal bacterial colonization, facilitating the migration of bacteria up the urethra and into the bladder, where they cause infections. The primary uropathogenic bacterium responsible for rUTIs is Escherichia coli (E. coli), accounting for 95% of UTIs, followed by Proteus mirabilis, Enterococcus faecalis, Staphylococcus saprophyticus, Staphylococcus epidermidis, and Klebsiella pneumoniae. An ideal solution for treating rUTIs in women would be to target a broad spectrum of uropathogenic bacteria, thereby preventing recurrent infections. Currently, the most common prophylactic approach for rUTIs involves the daily use of low-dose oral antibiotics, which have shown success in reducing symptomatic UTI recurrences. However, systemic circulation of these antibiotics often leads to adverse side effects, resulting in poor patient adherence to prescribed regimens. These challenges highlight the need for a prophylactic solution that delivers long-term therapy directly to the bladder, reducing the overall treatment burden on patients. Watershed Medical, Inc. is pioneering the development of an innovative drug delivery platform designed for local drug delivery in the bladder. The company has made substantial progress in creating an optimal prophylactic solution for rUTIs. Amikacin, a well-established antibiotic known for its safety and efficacy against E. coli, gram-negative bacteria, and Staphylococci species, was selected as the preferred antibiotic. Initial human studies have demonstrated that Watershed Medical’s product is retained in the bladder through multiple voiding cycles, remains comfortable, and can provide therapeutic Amikacin concentrations for at least 4 weeks and up to 3 months, all while not obstructing urine flow or bladder function. In this SBIR Phase I project, Watershed aims to make the entire drug delivery system capable of self-eliminating after the drug depot is depleted, thereby avoiding the need for additional procedures to remove the implant. The company plans to optimize the system for sustained release of Amikacin at therapeutic concentrations within the urinary bladder, with the added benefit of self-elimination once therapy is complete. This advancement represents a significant stride toward improving the quality of life for post-menopausal women dealing with rUTIs. The final product will allow for easy intravesical administration through the urethra into the bladder, extending drug release for up to 3 months to prevent UTIs. It will then self-eliminate on a similar timescale once the drug reserves are depleted, facilitating the excretion of all system components through urination without causing urethral obstruction.