Controlling Catheter-Associated Urinary Tract Infections Using Smart Catheters with Rationally Designed Active Topographies

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Catheter associated urinary tract infection (CAUTI) is one of the most common healthcare-associated infections (HAIs), with a prevalence of 13 – 15% in the United States. CAUTIs are also blamed for increased morbidity and mortality of affected patients with an estimated 13,000 deaths annually. It is well known that the abiotic catheter materials are prone to colonization of microbes, which then ascend the catheter via motility and biofilm formation, causing infections in the urinary tract. Due to the protection of the biofilm matrix and slow growth of attached cells, biofilm cells are up to 1,000 times more resistant to antimicrobials than the planktonic cells of the same species. Thus, CAUTIs are difficult to treat and blockage of the catheter lumen can occur especially during long-term use, leading to stone formation and infections of the bladder and even kidney. Treatment of CAUTIs with high doses of antimicrobial agents can also adversely promote the development of multidrug resistant bacteria. Despite extensive research to date, no current technology can provide long-term (>30 days) fouling control. This unmet challenge motivated us to engineer smart catheters to ultimately eradicate CAUTI. Recently, the PI’s lab developed a new antifouling strategy based on active topography that drives magnetically responsive micron-size pillars to beat with a tunable frequency and force level. This was achieved by loading Fe3O4 nanoparticles on the tip of each pillar and generating an electromagnetic field using an insulated copper coil embedded in the catheter wall (thus does not change the catheter profile). This novel design demonstrated unprecedented strong antifouling activities that can inhibit biofilm formation of multiple species by up to 3.6 logs (99.98%) for 48 hours and remove mature biofilms by up to 3.5 logs (99.97%) on demand with a stronger force, compared to the flat control. A prototype catheter with micron-size pillars on the inner wall was engineered and remained clean for more than 30 days under the flow of artificial urine and the challenge of uropathogenic Escherichia coli (UPEC), while both flat and static controls were completely blocked by UPEC biofilms within 5 days. These results motivated the team to further develop this technology to also control biofouling of the outer catheter wall, which is covered by urethral mucosa and involved in two thirds of CAUTIs. Integrated simulation and experimental studies will be conducted to understand the mechanism of biofouling control by active topography and the design principles for antifouling topographies on both sides of the catheter wall. The best design will be further tested in vivo using a rabbit model of CAUTI induced by UPEC. Both CAUTI prevention (up to 30 days) and removal of established biofilms will be evaluated.