title: 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.
abstract: Pseudomonas aeruginosais 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 thein vitroefficacy of urinary catheters impregnated with azithromycin (AZM) and ciprofloxacin (CIP) againstP. aeruginosaHere, we report how these coated catheters impact the course of CAUTI induced byP. aeruginosain 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 108CFU/ml of biofilm cells ofP. aeruginosaPAO1. AZM-CIP-coated implants (i) prevented biofilm formation on the implant's surface (P≤ 0.01), (ii) restricted bacterial colonization in the bladder and kidney (P< 0.0001), (iii) averted bacteriuria (P< 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< 0.001), myeloperoxidase (P< 0.05), reactive oxygen species (P≤ 0.001), and reactive nitrogen intermediates (P< 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-α), and IL-10 to the benefit of the host. Overall, the study demonstrates long-termin vivoeffectiveness of AZM-CIP-impregnated catheters, which may possibly be a key to success in preventing CAUTIs.
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh, India.
authors.forename: Hina
authors.initials: H
authors.lastname: Saini
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh, India.
authors.forename: Anitha
authors.initials: A
authors.lastname: Vadekeetil
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh, India.
authors.forename: Sanjay
authors.identifier: 0000-0003-2600-1450
authors.initials: S
authors.lastname: Chhibber
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh, India kusumharjai1961@gmail.com.
authors.forename: Kusum
authors.identifier: 0000-0002-5431-8183
authors.initials: K
authors.lastname: Harjai
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D055499:Catheter-Related Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D002939:Ciprofloxacin / Q000494:pharmacology*; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005260:Female; D005547:Foreign Bodies / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000382:microbiology; D062885:Urinary Catheters / Q000382:microbiology; D014552:Urinary Tract Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000900:Anti-Bacterial Agents; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; C556062:IL10 protein, mouse; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D016753:Interleukin-10; D002939:Ciprofloxacin; D017963:Azithromycin
keywords: quorum sensing; urinary tract infection