The application of ceragenins to orthopedic surgery and medicine

Abstract

Osteomyelitis and infections associated with orthopedic implants represent a significant burden of disease worldwide. Ceragenins (CSAs) are a relatively new class of small‐molecule antimicrobials that target a broad range of Gram‐positive and Gram‐negative bacteria as well as fungi, viruses, and parasites. This review sets the context of the need for new antimicrobial strategies by cataloging the common pathogens associated with orthopedic infection and highlighting the increasing challenges of managing antibiotic‐resistant bacterial strains. It then comparatively describes the antimicrobial properties of CSAs with a focus on the CSA‐13 family. More recently developed members of this family such as CSA‐90 and CSA‐131 may have a particular advantage in an orthopedic setting as they possess secondary pro‐osteogenic properties. In this context, we consider several new preclinical studies that demonstrate the utility of CSAs in orthopedic models. Emerging evidence suggests that CSAs are effective against antibiotic‐resistant Staphylococcus aureus strains and can prevent the formation of biofilms. There remains considerable scope for developing CSA‐based treatments, either as coatings for orthopedic implants or as local or systemic antibiotics to prevent bone infection.

Small Molecular Mimetics of Antimicrobial Peptides as a Promising Therapy To Combat Bacterial Resistance

“…Among these, CSA-90 (7) and CSA-131 (8) have the same MICs as 6 against the majority of selected bacterial pathogens but are slightly less active against P. aeruginosa. 70 None of the CSAs inhibited biofilm formation by various pathogens as effectively as the others, which was highly surprising.…”

From Marine Metabolites to the Drugs of the Future: Squalamine, Trodusquemine, Their Steroid and Triterpene Analogues

“…Ceragenin 186a exhibits bacterial killing activity against clinical isolates of S. aureus, including methicillin-resistant strains, P. aeruginosa present in cystic fibrosis sputa, and biofilms formed by different gram-positive and gram-negative bacteria [99,227]. These properties render ceragenins particularly useful in orthopedic medicine as antibiotics and implant coatings [228,229]. Silicone coating incorporating 186a developed by Williams et al [230] proved to be biocompatible, safe, and effective against MRSA biofilms in vivo [231,232].…”

Recent Progress in Bile Acid-Based Antimicrobials

“…2) to some extent . Ceragenins are not only resistant to protease degradation and salt sensitivity, but also have outstanding structure in controlling bacteria growth and preventing infection. − …”