The constantly increasing number of hemodialysis patients (2% increase every year in the United States) leadsto the subsequent increasing burden of catheter-related infections, with direct and indirect hospitalization costsranging between $17,000-$32,000 per episode and a mortality rate at 30 days of 18%. Current antimicrobialstrategies based on topical ointments lead to the selection of resistant bacterial strains, while lock solutions carrythe risk of thrombolytic and cardiac complications. Antibiotic (minocycline + rifampin)-coated catheters are ableto reduce the proliferation of Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis)but lack antimicrobial activity against Gram-negative (Pseudomonas aeruginosa) and fungal (Candida spp.)strains, while metal-based coatings (silver and its combination with other metals) have shown inconsistentbactericidal efficacy and the induction of adverse effects (e.g., pulmonary embolism). There is an urgent needfor an effective way to prevent and treat catheter-related infections. N8 Medical proposes an innovative coatingfor these catheters based on the use of ceragenins (CSAs), designed to mimic naturally occurring antimicrobialpeptides and their bactericidal capabilities. Moreover, CSAs permeabilize the membranes of bacterial cells andsensitize them to hydrophobic antibiotics. The coating will be designed to exert an anti-infective activity with theincorporation of CSAs, investigated in preliminary studies demonstrating its effectiveness against Gram-positive(methicillin-resistant S. epidermidis and S. aureus) and Gram-negative (P. aeruginosa) bacteria and fungalinfections (C. albicans), and to prevent the formation of biofilms. The antimicrobial activity of CSAs will promotethe complete eradication of bacterial populations (including resistant strains) responsible for catheter infections,reducing hospitalization costs and mortality rates. In this SBIR Phase I project, N8 Medical will develop a CSA-loaded, polyurethane-based hydrogel applicable to hemodialysis catheters and investigate its antimicrobialefficacy and CSA release profile in the context of direct contact with blood shear forces (Aim 1). The validatedcoated catheter will be tested in an animal model to assess its efficacy and safety (Aim 2). The success of thisproject will de-risk Phase II activities where the company will focus on preclinical, IDE-enabling safety,biocompatibility and efficacy studies against multiple challenge pathogens (Staphylococci, P. aeruginosa, C.albicans).
Public Health Relevance Statement: PROJECT NARRATIVE
Current preventive strategies are not able to eradicate bacterial proliferation, which occurs in up to 55% of
hemodialysis catheters, without engendering bacterial resistance. N8 Medical is developing a coating, which
incorporates N8 Medical's proprietary ceragenin technology, applicable to hemodialysis catheters. N8 Medical's
coating will prevent bacterial proliferation and biofilm formation, thereby reducing the need for colonized catheter
removal and replacement and the incidence of catheter-related bloodstream infections (CRBSI).
Project Terms:
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