To collate information on the incidence and nature of Urinary Tract Infection (UTI) in females, and to consider possible treatments based on clinical, translational and lab research.

Literature Review

Epidemiology
The opening chapter of the seventh International Consultation on Incontinence (1) describes the incidence of Urinary Incontinence (UI) and Faecal Incontinence (FI) as a function of health, maternal, and social factors. However Urinary tract Infection (UTI) was omitted. Women are significantly more likely to experience UTI than men (2), and their lifetime incidence of UTIs is reported to be 50-60%, with prevalence increasing with age (3). Among a cohort of 113 young women with UTI, 27% percent experienced at least one recurrence (rUTI) within six months (4). Catheter-associated UTI is the most common nosocomial infection, accounting for over a million cases at any one time in US hospitals and nursing homes (2). 

Microbiology
Uncomplicated human urinary tract infection (uUTI) is predominantly caused by Escherichia coli (5), however E. Faecalis and Staphylococcus saprophyticus have also been found (7) .   In catheter users, the Klebsiella and Proteus genera are present in the urine (3). In those with diabetes mellitus, Klebsiella, Enterobacter and candida genera are likely, with Enterococcus spp and candida spp also reported in complicated human UTI .  Additionally, Covid-19 caused cystitis and other LUTS (6).
Technology

GaniteTM is a Gallium Nitrate preparation proven to destroy biofilm-forming urinary pathogens in the lab (8) including a variety of E.Coli and P.Aeruginosa Strains. This research group have a patent for the intravesical instillation of the drug in humans and so clinical trial data is imminent. In rats a Foley catheter with an embedded fibre optic light guide delivered a photosensitiser and laser irradiation synergistically (9) demonstrating that the technology works, even at a small scale. Perhaps more realistically for an ambulant animal, a wireless LED device was implanted in a mouse given oral  5-Aminovulenic acid.  This treated lab-induced cancer over several days and is known as metronomic Photodynamic Therapy (PDT)(14). 

The optimal light and photosensitiser combinations for PDT of a variety of human infections  have been published by (10). For example, methylene blue and 660nm light is thought to kill Covid-19. PDT kills microbes regardless of their antibiotic resistance status and will not result in new forms of resistance.  The technique was recently employed in conjunction with antibiotics to treat UTI caused by e-coli (11). Lothar Lilge at al. (12) describe the intravesical instillation of a photosensitiser and fibre-optic delivery of green light during PDT for bladder cancer. The shape of the bladder, optical properties of the mucosal layer, and the geometry of illumination all influenced treatment efficacy. Castle and co-authors (13) describe the use of PDT, infrared laser therapy and bacterial interference in a cohort of patients with Neurogenic bladders and rUTI.

The technology to deliver PDT to bladders already exists but should be evaluated for human females with symptomatic UTI. Effective parameters are known for skin infection (10); however, they may require alteration for intravesical use necessitating further clinical research. 

The relatively simple treatment method of instilling a drug into to bladder is protected by at least one patent and so alternative versions may have to be researched.   However, the use of antibiotics with adjunctive pharmacy is emerging could halt the development of microbial resistance , suggesting they will remain a useful method of treatment in some situations. 

The research chapter of ICI consultation seven outlines the need for prevention and early intervention in UTI (15) .  The Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium aims to expand research beyond the detection and treatment of lower urinary tract symptoms (LUTS) to the promotion and preservation of bladder health and prevention of LUTS in girls and women (16). PDT has successfully prevented skin cancers (17) , and so over time an application for rUTI and related LUTs may emerge.

Several techniques are being developed for the treatment of infection to avoid overuse of antibiotics and the emergence of resistant microbes. PDT appears close to being ready for clinical use in UTI and may have roles in treatment and prevention.