CSA-90 reduces periprosthetic joint infection in a novel rat model challenged with local and systemic Staphylococcus aureus
(2020) In Journal of Orthopaedic Research 38(9). p.2065-2073- Abstract
Infection of orthopedic implants is a growing clinical challenge to manage due to the proliferation of drug-resistant bacterial strains. In this study, we aimed to investigate whether the treatment of implants with ceragenin-90 (CSA-90), a synthetic compound based on endogenous antibacterial peptides, could prevent infection in a novel rat model of periprosthetic joint infection (PJI) challenged with either local or systemic Staphylococcus aureus. A novel preclinical model of PJI was created using press-fit porous titanium implants in the distal femur of male Wistar rats. Sterile implants were pre-treated with 500 μg CSA-90 in saline. S. aureus was applied either directly at the time of surgery or administered via tail vein injection... (More)
Infection of orthopedic implants is a growing clinical challenge to manage due to the proliferation of drug-resistant bacterial strains. In this study, we aimed to investigate whether the treatment of implants with ceragenin-90 (CSA-90), a synthetic compound based on endogenous antibacterial peptides, could prevent infection in a novel rat model of periprosthetic joint infection (PJI) challenged with either local or systemic Staphylococcus aureus. A novel preclinical model of PJI was created using press-fit porous titanium implants in the distal femur of male Wistar rats. Sterile implants were pre-treated with 500 μg CSA-90 in saline. S. aureus was applied either directly at the time of surgery or administered via tail vein injection immediately afterward. Animals were monitored daily for clinical and radiographic evidence of infection for a total of 6 weeks. Post-study microbiological, radiographic, and histological analysis were performed to determine the incidence of PJI and assess osseointegration. CSA-90 treated groups demonstrated a reduced rate of PJI as confirmed by deep tissue swab culture at the time of cull compared with untreated groups with both local (33% vs 100%; P =.009) and systemic (10% vs 90%; P <.0001) S. aureus inoculation. Median survival time also increased from 8 to 17 days and from 8 to 42 days, respectively. In conclusion, this study describes a novel preclinical model of local and hematogenous PJI using a porous metal implant. CSA-90 reduced the incidence of PJI in this model supporting its further development as an antimicrobial coating for orthopedic implants.
(Less)
- author
- Mills, Rebecca J. ; Boyling, Alexandra ; Cheng, Tegan L. ; Peacock, Lauren ; Savage, Paul B. ; Tägil, Magnus LU ; Little, David G. and Schindeler, Aaron
- publishing date
- 2020-02-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CSA-90, hematogenous, osseointegration, periprosthetic joint infection, preclinical model, Staphylococcus aureus
- in
- Journal of Orthopaedic Research
- volume
- 38
- issue
- 9
- pages
- 2065 - 2073
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85079402981
- pmid:32009241
- ISSN
- 0736-0266
- DOI
- 10.1002/jor.24618
- language
- English
- LU publication?
- no
- id
- 7abf2eca-7e9b-42b9-83bb-05f4eda8358a
- date added to LUP
- 2020-02-28 10:34:44
- date last changed
- 2024-05-01 05:43:19
@article{7abf2eca-7e9b-42b9-83bb-05f4eda8358a,
abstract = {{<p>Infection of orthopedic implants is a growing clinical challenge to manage due to the proliferation of drug-resistant bacterial strains. In this study, we aimed to investigate whether the treatment of implants with ceragenin-90 (CSA-90), a synthetic compound based on endogenous antibacterial peptides, could prevent infection in a novel rat model of periprosthetic joint infection (PJI) challenged with either local or systemic Staphylococcus aureus. A novel preclinical model of PJI was created using press-fit porous titanium implants in the distal femur of male Wistar rats. Sterile implants were pre-treated with 500 μg CSA-90 in saline. S. aureus was applied either directly at the time of surgery or administered via tail vein injection immediately afterward. Animals were monitored daily for clinical and radiographic evidence of infection for a total of 6 weeks. Post-study microbiological, radiographic, and histological analysis were performed to determine the incidence of PJI and assess osseointegration. CSA-90 treated groups demonstrated a reduced rate of PJI as confirmed by deep tissue swab culture at the time of cull compared with untreated groups with both local (33% vs 100%; P =.009) and systemic (10% vs 90%; P <.0001) S. aureus inoculation. Median survival time also increased from 8 to 17 days and from 8 to 42 days, respectively. In conclusion, this study describes a novel preclinical model of local and hematogenous PJI using a porous metal implant. CSA-90 reduced the incidence of PJI in this model supporting its further development as an antimicrobial coating for orthopedic implants.</p>}},
author = {{Mills, Rebecca J. and Boyling, Alexandra and Cheng, Tegan L. and Peacock, Lauren and Savage, Paul B. and Tägil, Magnus and Little, David G. and Schindeler, Aaron}},
issn = {{0736-0266}},
keywords = {{CSA-90; hematogenous; osseointegration; periprosthetic joint infection; preclinical model; Staphylococcus aureus}},
language = {{eng}},
month = {{02}},
number = {{9}},
pages = {{2065--2073}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Orthopaedic Research}},
title = {{CSA-90 reduces periprosthetic joint infection in a novel rat model challenged with local and systemic Staphylococcus aureus}},
url = {{http://dx.doi.org/10.1002/jor.24618}},
doi = {{10.1002/jor.24618}},
volume = {{38}},
year = {{2020}},
}