Azithromycin-Ciprofloxacin Impregnated Urinary Catheters Avert Bacterial Colonization, Biofilm Formation and Inflammation in a Murine Model of Foreign-Body Associated Urinary Tract Infections Caused by Pseudomonas aeruginosa

Pseudomonas aeruginosa is a multifaceted pathogen causing a variety of biofilm-mediated infections including catheter-associated urinary tract infections (CAUTIs). High prevalence of CAUTIs in hospitals, their clinical manifestations like urethritis, cystitis, pyelonephritis, meningitis, urosepsis, death; and economic challenges underscore the need for management of these infections. Biomaterial modification of urinary catheters with dual drugs seems an interesting approach to combat CAUTIs by inhibiting biofilm. Previously, we demonstrated in-vitro efficacy of azithromycin (AZM) and ciprofloxacin (CIP) impregnated urinary catheters 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-CIP coated silicone implants in the bladder, followed by transurethral inoculation of 10(8) CFU/ml of biofilm cells of P. aeruginosa PAO1. AZM-CIP implants a) prevented biofilm formation on implant's surface (P≤0.01); b) restricted bacterial colonization in bladder and kidney (P <0.0001); c) averted bacteriuria (P<0.0001) and d) exhibited no major histopathological changes for 28 days as compared to uncoated implants which showed persistent CAUTI. Antibiotics implant also overcame implant-mediated inflammation as characterised by trivial levels of inflammatory markers like malondialdehyde (P<0.001), myeloperoxidase (P<0.05), reactive oxygen species (P≤0.001) and reactive nitrogen intermediates (P<0.01) vis-à-vis uncoated implants. Further, AZM-CIP implants showed immunomodulation by manipulating the release of inflammatory cytokines IL-6, TNF-α and IL-10 to the benefit of 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.

Antimicrobial agents and chemotherapy. 2016 Dec 28 [Epub ahead of print]

Hina Saini, Anitha Vadekeetil, Sanjay Chhibber, Kusum Harjai

Department of Microbiology, Panjab University, Chandigarh, India., Department of Microbiology, Panjab University, Chandigarh, India .

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