title: Prevention of Staphylococcus aureus biomaterial-associated infections using a polymer-lipid coating containing the antimicrobial peptide OP-145.
abstract: The scarcity of current antibiotic-based strategies to prevent biomaterial-associated infections (BAI) and their risk of resistance development prompted us to develop a novel antimicrobial implant-coating to prevent Staphylococcus aureus-induced BAI. We incorporated the antimicrobial peptide OP-145 into a Polymer-Lipid Encapsulation MatriX (PLEX)-coating to obtain high peptide levels for prolonged periods at the implant-tissue interphase. We first confirmed that OP-145 was highly effective in killing S. aureus and inhibiting biofilm formation in vitro. OP-145 injected along S. aureus-inoculated implants in mice significantly reduced the number of culture-positive implants. OP-145 was released from the PLEX coating in a controlled zero-order kinetic rate after an initial 55%-burst release and displayed bactericidal activity in vitro. In a rabbit intramedullary nail-related infection model, 67% of rabbits with PLEX-OP-145-coated nails had culture-negative nails after 28days compared to 29% of rabbits with uncoated nails. In rabbits with PLEX-OP-145-coated nails, bone and soft tissue samples were culture-negative in 67% and 80%, respectively, whereas all bone samples and 71% of the soft tissue samples of rabbits with uncoated nails were infected. Together, PLEX-OP-145 coatings, of which both compounds have already been found safe in man, can prevent implant colonization and S. aureus-induced BAIs.
authors.affiliation: Dept. of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, P.O. Box 9600, RC Leiden, The Netherlands. Electronic address: a.de_breij@lumc.nl.
authors.forename: A
authors.initials: A
authors.lastname: de Breij
authors.affiliation: Dept. of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Riool
authors.affiliation: Dept. of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: P H S
authors.initials: PH
authors.lastname: Kwakman
authors.affiliation: Dept. of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: de Boer
authors.affiliation: Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, P.O. Box 9600 RC Leiden, the Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Cordfunke
authors.affiliation: Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, P.O. Box 9600 RC Leiden, the Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Drijfhout
authors.affiliation: PolyPid Ltd., 18 Hasivim, St. Petach-Tikva 4959376, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Cohen
authors.affiliation: PolyPid Ltd., 18 Hasivim, St. Petach-Tikva 4959376, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Emanuel
authors.affiliation: Dept. of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: S A J
authors.initials: SA
authors.lastname: Zaat
authors.affiliation: Dept. of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, P.O. Box 9600, RC Leiden, The Netherlands.
authors.forename: P H
authors.initials: PH
authors.lastname: Nibbering
authors.affiliation: AO Research Institute Davos, AO Foundation, Clavadelerstrasse 8 Davos Platz, CH7270 Davos, Switzerland.
authors.forename: T F
authors.initials: TF
authors.lastname: Moriarty
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000627:therapeutic use; D018441:Biofilms; D002784:Cholesterol / Q000737:chemistry; D005260:Female; D019344:Lactic Acid / Q000737:chemistry; D008810:Mice, Inbred C57BL; D009260:Nail Diseases / Q000188:drug therapy; D010713:Phosphatidylcholines / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019736:Prostheses and Implants; D011817:Rabbits; D012828:Silicones / Q000737:chemistry; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C000611832:OP-145 peptide; D010713:Phosphatidylcholines; D012828:Silicones; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D015060:1,2-Dipalmitoylphosphatidylcholine; D019344:Lactic Acid; D002784:Cholesterol; C010942:1,2-distearoyllecithin
keywords: Antimicrobial coating; Antimicrobial peptides; OP-145; Orthopaedic implant; Rabbit; Staphylococcus aureus