Nitric oxide-releasing balloon inflation fluid for Foley catheters to prevent catheter-associated urinary tract infections

ABSTRACT Catheter-associated urinary tract infections (CAUTIs) are the most prevalent nosocomial infections. These infections impose a significant financial burden on the healthcare system and are responsible for approximately 15,000 deaths each year in the US. CAUTIs are caused by free-floating bacteria that adhere to the surface of Foley catheters and the patient’s uroepithelium, forming protective biofilms that enhance bacterial survival and resistance. In this study, a nitric oxide (NO)-releasing liquid formulation is used to inflate the Foley catheter balloon, aiming to inhibit biofilm formation and reduce the risk of CAUTIs. The solution of S-nitrosoglutathione (GSNO), an endogenous NO donor molecule, was used as the catheter inflation fluid. To assess the NO-release profile, the GSNO was dissolved in various pH-adjusted (pH 6.5) aqueous media (deionized water, phosphate-buffered saline, and 2-[4-(2-hydroxyethyl)piperazine-1-yl]ethanesulfonic acid [HEPES] buffers). The GSNO/HEPES formulation sustained NO fluxes through the inflated balloon wall above 0.5 × 10⁻¹⁰ mol·min⁻¹·cm⁻² for up to 10 days, as well as significantly reduced the planktonic bacteria counts and surface colonization against Escherichia coli . The safety of the optimized GSNO formulation was evaluated in vivo in a 7-day preclinical porcine model. The formulation showed no signs of NO-related toxicity. Overall, this study presents a promising, translatable approach to substantially reducing the risk of CAUTIs in healthcare settings. IMPORTANCE Catheter-associated urinary tract infections (CAUTIs) are the most frequent hospital-acquired infections and pose serious risks for patients with Foley catheters in hospitals, nursing homes, and other care facilities. These infections lead to significant mortality and healthcare expenses and are especially difficult to prevent due to bacterial biofilms on catheter surfaces. Our study introduces a novel solution, a nitric oxide (NO)-releasing balloon inflation fluid using S-nitrosoglutathione (GSNO), that continuously releases antimicrobial NO for up to 10 days. This approach significantly reduces bacterial counts and surface colonization by Escherichia coli , a main cause of CAUTIs, while demonstrating safety in preclinical animal testing. Our findings suggest that this strategy could reduce infection risk and improve outcomes for catheterized patients across diverse healthcare settings.