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Experimental Endocarditis Model of Methicillin Resistant Staphylococcus aureus (MRSA) in Rat
Published on: June 4, 2012
Comparable efficacies of the antimicrobial peptide human lactoferrin 1-11 and gentamicin in a chronic
Christopher Faber1, Hein P Stallmann, D M Lyaruu
1Department of Orthopaedic Surgery, VU University Medical Center, P. O. Box 7057, 1007 MB Amsterdam, The Netherlands.
Abstract:
The therapeutic efficacy of an antimicrobial peptide, human lactoferrin 1-11 (hLF1-11), was investigated in a model of chronic methicillin-resistant Staphylococcus aureus (MRSA) (gentamicin susceptible) osteomyelitis in rabbits. We incorporated 50 mg hLF1-11/g or 50 mg gentamicin/g cement powder into a calcium phosphate bone cement (Ca-P) and injected it into the debrided tibial cavity, creating a local drug delivery system. The efficacy of hLF1-11 and gentamicin was compared to that of a sham-treated control (plain bone cement) (n=6) and no treatment (infected only) (n=5). The results were evaluated by microbiology, radiology, and histology. MRSA was recovered from all tibias in both control groups (n=11). On the other hand, hLF1-11 and gentamicin significantly reduced the bacterial load. Furthermore, no growth of bacteria was detected in five out of eight and six out of eight specimens of the hLF1-11- and gentamicin-treated groups, respectively. These results were confirmed by a significant reduction of the histological disease severity score by hLF1-11 and gentamicin compared to both control groups. The hLF1-11-treated group also had a significantly lower radiological score compared to the gentamicin-treated group. This study demonstrates the efficacy of hLF1-11 incorporated into Ca-P bone cement as a possible therapeutic strategy for the treatment of osteomyelitis, showing efficacy comparable to that of gentamicin. Therefore, the results of this study warrant further preclinical investigations into the possibilities of using hLF1-11 for the treatment of osteomyelitis.
Insights
Human lactoferrin 1-11 (hLF1-11) in bone cement effectively treated chronic MRSA osteomyelitis in rabbits, showing results comparable to gentamicin.
Area of Science:
- Biomedical Engineering
- Infectious Diseases
- Pharmacology
Background:
- Chronic osteomyelitis, particularly due to methicillin-resistant Staphylococcus aureus (MRSA), presents a significant therapeutic challenge.
- Current treatments often involve systemic antibiotics with limited efficacy and potential side effects.
- Novel local drug delivery systems are needed to improve treatment outcomes for bone infections.
Purpose of the Study:
- To evaluate the therapeutic efficacy of human lactoferrin 1-11 (hLF1-11) incorporated into calcium phosphate bone cement (Ca-P) for treating chronic MRSA osteomyelitis.
- To compare the efficacy of hLF1-11 with gentamicin, a standard antibiotic, in a rabbit model.
- To assess the potential of hLF1-11 as a local therapeutic agent for osteomyelitis.
Main Methods:
- A rabbit model of chronic MRSA osteomyelitis was established.
- hLF1-11 or gentamicin (50 mg/g) was incorporated into Ca-P bone cement and injected into the debrided tibial cavity.
- Control groups received plain bone cement or no treatment.
- Efficacy was evaluated using microbiological, radiological, and histological analyses.
Main Results:
- MRSA was eradicated in 5/8 hLF1-11 treated tibias and 6/8 gentamicin treated tibias.
- Both hLF1-11 and gentamicin significantly reduced bacterial load and histological disease severity compared to controls.
- The hLF1-11 group showed a significantly lower radiological score than the gentamicin group.
Conclusions:
- hLF1-11 incorporated into Ca-P bone cement demonstrates significant therapeutic efficacy against MRSA osteomyelitis in a rabbit model.
- The efficacy of hLF1-11 is comparable to that of gentamicin, suggesting its potential as an alternative treatment.
- Further preclinical studies are warranted to explore hLF1-11 for osteomyelitis treatment.

