title: Model development for determining the efficacy of a combination coating for the prevention of perioperative device related infections: a pilot study.
abstract: 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.
authors.affiliation: Department of Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah; Department of Orthopaedics, University of Utah, Salt Lake City, Utah.
authors.forename: Kristofer D
authors.initials: KD
authors.lastname: Sinclair
authors.forename: Theresa X
authors.initials: TX
authors.lastname: Pham
authors.forename: Dustin L
authors.initials: DL
authors.lastname: Williams
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Farnsworth
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Loc-Carrillo
authors.forename: Roy D
authors.initials: RD
authors.lastname: Bloebaum
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D008422:Materials Testing / Q000379:methods; D055624:Methicillin-Resistant Staphylococcus aureus / Q000254:growth & development*; D010865:Pilot Projects; D019736:Prostheses and Implants; D012756:Sheep; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013256:Steroids / Q000494:pharmacology*; D014025:Titanium / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D020099:Coated Materials, Biocompatible; D013256:Steroids; C521528:ceragenin CSA-13; D014025:Titanium
keywords: animal model; antimicrobial; controlled drug release; titanium; total joint replacement