Back to Search
Start Over
Local delivery of the cationic steroid antibiotic CSA-90 enables osseous union in a rat open fracture model of Staphylococcus aureus infection.
- Source :
-
The Journal of bone and joint surgery. American volume [J Bone Joint Surg Am] 2015 Feb 18; Vol. 97 (4), pp. 302-9. - Publication Year :
- 2015
-
Abstract
- Background: Treatment of infected open fractures remains a major clinical challenge. In this study, we investigated the novel broad-spectrum antibiotic CSA-90 (cationic steroid antibiotic-90) as an antimicrobial agent.<br />Methods: CSA-90 was screened in an osteoblast cell culture model for effects on differentiation and mineralization. Local delivery of CSA-90 was then tested alone and in combination with recombinant human bone morphogenetic protein-2 (rhBMP-2) in a mouse ectopic bone formation model (n=40 mice) and in a rat open fracture model inoculated with pathogenic Staphylococcus aureus (n=84 rats).<br />Results: CSA-90 enhanced matrix mineralization in cultured osteoblasts and increased rhBMP-2-induced bone formation in vivo. All animals in which an open fracture had been inoculated with Staphylococcus aureus and not treated with local CSA-90, including those treated with rhBMP-2, had to be culled prior to the experimental end point (six weeks) because of localized osteolysis and deterioration of overall health, whereas CSA-90 prevented establishment of infection in all open fractures in which it was used (p≤0.012). Increased union rates were seen for the fractures treated with rhBMP-2 or with the combination of rhBMP-2 and CSA-90 compared with that observed for the fractures treated with CSA-90 alone (p=0.04).<br />Conclusions: CSA-90 can promote osteogenesis and be used for prevention of Staphylococcus aureus infection in preclinical models.<br />Clinical Relevance: Local delivery of CSA-90 represents a novel strategy for prevention of infection and may have specific benefits in the context of orthopaedic injuries.<br /> (Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.)
- Subjects :
- Analysis of Variance
Animals
Bone Morphogenetic Proteins administration & dosage
Calcification, Physiologic drug effects
Cells, Cultured
Choristoma drug therapy
Choristoma pathology
Disease Models, Animal
Female
Femoral Fractures diagnostic imaging
Fractures, Open diagnostic imaging
Humans
Mice
Mice, Inbred C57BL
Osteitis microbiology
Osteoblasts drug effects
Osteogenesis drug effects
Radiography
Rats
Staphylococcal Infections microbiology
Staphylococcus aureus
Anti-Bacterial Agents administration & dosage
Antimicrobial Cationic Peptides administration & dosage
Femoral Fractures complications
Fracture Healing drug effects
Fractures, Open complications
Osteitis drug therapy
Pregnanes administration & dosage
Propylamines administration & dosage
Staphylococcal Infections drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1535-1386
- Volume :
- 97
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of bone and joint surgery. American volume
- Publication Type :
- Academic Journal
- Accession number :
- 25695982
- Full Text :
- https://doi.org/10.2106/JBJS.N.00840