ceragenin-csa-13 and Staphylococcal-Infections

Antibiotic resistant bacterial infections are a growing problem in patient care. These infections are difficult to treat and severely affect the patient's quality of life. The goal of this translational experiment was to investigate the antimicrobial potential of cationic steroidal antimicrobial-13 (CSA-13) for the prevention of perioperative device-related infections in vivo. It was hypothesized that when incorporated into a polymeric device coating, the release of CSA-13 could prevent perioperative device-related infection without inhibiting skeletal attachment. To test this hypothesis, 12 skeletally mature sheep received a porous coated titanium implant in the right femoral condyle. Group 1 received the titanium implant and an inoculum of 5 × 10(8) CFU of methicillin-resistant Staphylococcus aureus (MRSA). Group 2 received a CSA-13 coated implant and the MRSA inoculum. Group 3 received only the CSA-13 coated implant and Group 4 received only the implant-without the CSA-13 coating or MRSA inoculum. In conclusion, the CSA-13 combination coating demonstrated bactericidal potential without adversely affecting skeletal attachment. The CSA-13 containing groups exhibited no evidence of bacterial infection at the conclusion of the 12 week study and established skeletal attachment consistent with Group 4. In contrast, all of the Group 1 animals became infected and required euthanasia within 6-10 days. The significance of this finding is that this combination coating could be applied to implanted devices to prevent perioperative device-related infections. This method may facilitate significantly reduced incidences of device-related infections as well as a new method to treat and prevent resistant strain bacterial infections.

Topics: Animals; Anti-Infective Agents; Coated Materials, Biocompatible; Materials Testing; Methicillin-Resistant Staphylococcus aureus; Pilot Projects; Prostheses and Implants; Sheep; Staphylococcal Infections; Steroids; Titanium

We provided contact lens hydrogels with an antibacterial innate immune function using nonpeptide mimics of endogenous antimicrobial peptides.. Antimicrobial peptide mimics, ceragenins, were prepared for either covalent attachment to hydrogels or for controlled elution from lenses. The lipophilicity of the ceragenins was varied incrementally to provide differing levels of association with hydrophobic domains in lenses. Ceragenin-containing lenses were challenged repeatedly with Staphylococcus aureus or Pseudomonas aeruginosa in nutrient media. Bacterial growth and biofilm formation on lenses were quantified.. A ceragenin covalently fixed in lenses effectively inhibited S. aureus biofilm formation on lenses in 10% tryptic soy broth (approximately 3-log reduction), but did not reduce biofilm formation in 100% tryptic soy broth. Ceragenins designed to elute from lenses were incorporated at 1% relative to the dry weight of the lenses. The ceragenin with the optimal lipid content, CSA-138, prevented bacterial colonization of lenses for 15 days with P. aeruginosa and for 30 days with S. aureus (daily exchange of growth media and reinoculation with 10⁶ CFU). Measurement of CSA-138 elution showed that concentrations of the ceragenin never exceeded 5 μg/mL in a 24-hour period and that after 4 days of elution, concentrations dropped to <0.5 μg/mL, while maintaining antibacterial activity.. Ceragenin CSA-138 appears well suited for providing an innate immune-like function to abiotic hydrogel contact lenses for extended periods of time. Elution of even low concentrations of CSA-138 (<0.5 μg) is sufficient to eliminate inocula of 10⁶ CFU of S. aureus and P. aeruginosa.

Topics: Anti-Infective Agents; Biofilms; Contact Lenses, Hydrophilic; Eye Infections, Bacterial; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate; Hydrophobic and Hydrophilic Interactions; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Steroids

More than 400,000 primary hip and knee replacement surgeries are performed each year in the United States. From these procedures, approximately 0.5-3% will become infected and when considering revision surgeries, this rate has been found to increase significantly. Antibiotic-resistant bacterial infections are a growing problem in patient care. This in vitro research investigated the antimicrobial potential of the polymer released, broad spectrum, Cationic Steroidal Antimicrobial-13 (CSA-13) for challenges against 5 × 10(8) colony forming units (CFU) of methicillin-resistant Staphylococcus aureus (MRSA). It was hypothesized that a weight-to-weight (w/w) concentration of 18% CSA-13 in silicone would exhibit potent bactericidal potential when used as a controlled release device coating. When incorporated into a polymeric device coating, the 18% (w/w) broad-spectrum polymer released CSA-13 antimicrobial eliminated 5 × 10(8) CFU of MRSA within 8 h. In the future, these results will be utilized to develop a sheep model to assess CSA-13 for the prevention of perioperative device-related infections in vivo.

Topics: Anti-Infective Agents; Coated Materials, Biocompatible; Colony Count, Microbial; Drug Resistance, Bacterial; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Polymers; Porosity; Staphylococcal Infections; Steroids; Time Factors