Pseudomonas aeruginosa is a multifaceted pathogen causing a variety of biofilm-mediated infections, including catheter-associated urinary tract infections (CAUTIs). The high prevalence of CAUTIs in hospitals, their clinical manifestations, such as urethritis, cystitis, pyelonephritis, meningitis, urosepsis, and death, and the associated economic challenges underscore the need for management of these infections. Biomaterial modification of urinary catheters with two drugs seems an interesting approach to combat CAUTIs by inhibiting biofilm. Previously, we demonstrated the in vitro efficacy of urinary catheters impregnated with azithromycin (AZM) and ciprofloxacin (CIP) against P. aeruginosa. Here, we report how these coated catheters impact the course of CAUTI induced by P. aeruginosa in a murine model. CAUTI was established in female LACA mice with uncoated or AZM-CIPcoated silicone implants in the bladder, followed by transurethral inoculation of 10 8 CFU/ml of biofilm cells of P. aeruginosa PAO1. AZM-CIP-coated implants (i) prevented biofilm formation on the implant's surface (P Յ 0.01), (ii) restricted bacterial colonization in the bladder and kidney (P Ͻ 0.0001), (iii) averted bacteriuria (P Ͻ 0.0001), and (iv) exhibited no major histopathological changes for 28 days in comparison to uncoated implants, which showed persistent CAUTI. Antibiotic implants also overcame implant-mediated inflammation, as characterized by trivial levels of inflammatory markers such as malondialdehyde (P Ͻ 0.001), myeloperoxidase (P Ͻ 0.05), reactive oxygen species (P Յ 0.001), and reactive nitrogen intermediates (P Ͻ 0.01) in comparison to those in uncoated implants. Further, AZM-CIP-coated implants showed immunomodulation by manipulating the release of inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-␣), and IL-10 to the benefit of the host. Overall, the study demonstrates long-term in vivo effectiveness of AZM-CIP-impregnated catheters, which may possibly be a key to success in preventing CAUTIs.KEYWORDS quorum sensing, urinary tract infection H ealth care facilities employ various invasive devices like vascular or urinary catheters (UCs), ventilators, cardiac valves, and implants for medical procedures meant for the benefit of patients. However, infection of these very devices complicates the treatment of hospitalized patients, resulting in health care-associated infections (HAIs). Urinary tract infection (UTI) is one of the most common types of HAI, and around 75 to 80% of hospital-acquired UTIs are related to urinary catheterization (1). Urethral cath-