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Catheter–associated urinary tract infections (CAUTIs) cause millions of infections in the US every year, with direct medical costs exceeding billions of dollars and resulting in > 1 million ER visits and hospitalizations, resulting in thousands of deaths. CAUTI is thought to be a major reservoir both containing and creating highly drug-resistant infections, due to the chronicity of infection, biofilm formation, and the setting of institutionalization with chronic exposure to antibiotics, thus enabling resistance.
To reduce antibiotic resistance developing in this setting, we are attempting to apply both antimicrobial photodynamic therapy (aPDT), antimicrobial blue light (aBL), and combinations of both with minimal use of antibiotics. To this end, we established a rat model of UTI. In this model, we catheterized female rats, infected them with a standard uropathogenic E.Coli (UPEC; UTI89), infused the bladder with methylene blue (MB) and potassium Iodide (KI), and illuminated the bladder once with a diffusing fiber connected to a 1W 660nm laser. Multilog killing was observed, but given the transient nature of ROS generation, regrowth of UPEC was seen 24 hours later. To this end, we are experimenting with the combination of illumination with antibiotics. When tetracyclines are illuminated by aBL, we have found > 6 log(10) steps of microbial killing in vitro, and significant drops in the antibiotic MIC effected by the combination of light and drug. Multiple treatments with aBL and aPDT both with and without limited intravesical application of antimicrobials may light the way to solving this problem.
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