Ceragenin-based antimicrobial coating to tackle hemodialysis catheter-related infections.

PROJECT SUMMARY The constantly increasing number of hemodialysis patients (2% increase every year in the United States) leads to the subsequent increasing burden of catheter-related infections, with direct and indirect hospitalization costs ranging between $17,000-$32,000 per episode and a mortality rate at 30 days of 18%. Current antimicrobial strategies based on topical ointments lead to the selection of resistant bacterial strains, while lock solutions carry the risk of thrombolytic and cardiac complications. Antibiotic (minocycline + rifampin)-coated catheters are able to 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 inconsistent bactericidal efficacy and the induction of adverse effects (e.g., pulmonary embolism). There is an urgent need for an effective way to prevent and treat catheter-related infections. N8 Medical proposes an innovative coating for these catheters based on the use of ceragenins (CSAs), designed to mimic naturally occurring antimicrobial peptides and their bactericidal capabilities. Moreover, CSAs permeabilize the membranes of bacterial cells and sensitize them to hydrophobic antibiotics. The coating will be designed to exert an anti-infective activity with the incorporation 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 fungal infections (C. albicans), and to prevent the formation of biofilms. The antimicrobial activity of CSAs will promote the 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 antimicrobial efficacy and CSA release profile in the context of direct contact with blood shear forces (Aim 1). The validated coated catheter will be tested in an animal model to assess its efficacy and safety (Aim 2). The success of this project 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).