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Synergistic Photodynamic Therapy for Catheter-Associated Urinary Tract Infection in Rats

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Sources of Funding: R21/R33AI121700 (Synergistic Photodynamic Therapy for Urinary Tract Infections)_x000D_

Introduction

The rise of multi-drug resistant strains of uropathogenic bacteria is increasing the number of catheter-associated urinary tract infections (CAUTIs), which affect more than one million people per year in the U.S., that are untreatable with current antibiotics. The increase of antibiotic resistance necessitates the need for new antimicrobial treatments that will be effective against multidrug-resistant strains and will not themselves induce resistance. The aim of our study is to demonstrate the feasibility of in vivo treatment of urinary tract infections in rats using photodynamic inactivation (PDI); a method of treatment which uses non-toxic dyes, called photosensitizers, excited with harmless visible light to react with ambient oxygen to produce reactive oxygen species that selectively destroy infecting bacteria while preserving host tissue._x000D_ _x000D_ _x000D_

Methods

One mL of stable luciferase (lux)-expressing UPEC was inoculated into the bladder of anesthetized female rats via 20 guage angiocatheter placed in the urethra. The progression of the infection and treatment was monitored non-invasively in real time using bioluminescence imaging. The bladder infections in 10 rats were treated by installation of MB [100uM] and KI [100mM] solution after wthich the bladder was illuminated using an optic fiber with 660 nm laser light for 30mins. Serial daily imaging was conducted to document the duration of infection. This was compared to a control group of rats who were infected with UPEC but not treated as well as a group of UPEC infected rats treated only with MB.

Results

Synergistic UPEC killing effect of PDI (MB + KI) was observed in the PDI treatment group, which demonstrated faster resolution of infection when compared to the control group and MB only group.

Conclusions

As both MB and KI are approved for use in the human bladder, an ideal application of this technology would be the treatment of CAUTI in chronically catheterized patients by illuminating MB and KI solution using a laser-coupled catheter with embedded fiber optic light guide called a “photonic Foley catheter.� Our study demonstrates the feasibility of in vivo PDI as a novel approach to treatment of urinary tract infections, which merits further investigation._x000D_

Funding

R21/R33AI121700 (Synergistic Photodynamic Therapy for Urinary Tract Infections)_x000D_

Authors
Anton Wintner
Yingying Huang
Jeffrey Gelfand
Francis McGovern
Michael Hamblin
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