Executive Summary : | Catheter-associated urinary tract infection (CAUTI) is one of the most common nosocomial infections associated with high morbidity and mortality. About one-third of all medical device-associated infections are related to urinary catheterization. The high incidences of CAUTI in hospitals, their clinical manifestations, for example, urethritis, cystitis, pyelonephritis, urosepsis, and death, and the related economic loss emphasize the need for the prevention of these infections. The quantum of microbial infections depends on the duration of catheterization. In clinical practice, 10−50% of patients during short-term catheterization (less than 7 days) develop urinary tract infections (UTI), and approximately all patients undergoing long-term catheterization (more than 28 days) got infected. The major cause of CAUTI is the susceptibility of the urinary tract catheter (UTC) material surface towards bacterial adhesion and biofilm formation leading to bacteriuria and UTI. Although antibiotic-coated catheters are found to be effective in controlling CAUTI, consistent exposure to antibiotics in long-term catheters poses the risk of the development and spread of multi-drug resistant microbial strains. The main aim of this proposal is to design an antibiotic-free material-based strategy to develop antimicrobial UTC. A ternary composite system of polydopamine (PDA), metal ions (Mn+= Ag+, Cu2+), and antimicrobial polymer epsilon-polylysine (EPL) will be utilized to design antimicrobial coatings on both the inner and outer surface of UTC via wet chemistry methods. Detailed surface characterization of the uncoated and coated UTC will be performed in terms of its chemistry, morphology, roughness, coating thickness, wettability, and aqueous/urine durability. The coated catheters will be evaluated for their antimicrobial potential using broth microdilution and bacterial viability studies. In-vitro assessment of the designed catheters will be performed for their anti-biofilm, anti-fouling, and anti-encrustation properties. The coated catheters will also be tested for their biocompatibility against primary human urinary bladder epithelial cells. The best-performed catheters will be evaluated for their in-vivo safety using the rabbit model of CAUTI. A clinically relevant in vitro CAUTI bladder model will be used to verify the efficiency of the coated catheters against bacteriuria and bacterial migration. Successful completion of the proposed work will unveil a new mechanism for preventing microbial contamination by designing EPL-Mn+-PDA Nanocoatings and the methodology can be further extended to other areas (e.g., other biomedical indwelling devices, food and beverage industries) wherein microbial adhesion and biofilm formation is a huge problem. The chemical formulation can also be used to design antiseptic solutions to prevent healthcare-associated infections. |