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Development of an innovative in vivo model of PJI treated with DAIR
Hervé Poilvache1,2,3, Françoise Van Bambeke2, Olivier Cornu1,3
1Neuro Musculo-Skeletal Laboratory, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium.
Introduction:
Prosthetic Joint Infection (PJI) are catastrophic complications of joint replacement. Debridement, implant retention, and antibiotic therapy (DAIR) is the usual strategy in acute infections but fails in 45% of MRSA infections. We describe the development of a model of infected arthroplasty in rabbits, treated with debridement and a course of vancomycin with clinically relevant dosage.
Materials And Methods:
A total of 15 rabbits were assigned to three groups: vancomycin pharmacokinetics (A), infection (B), and DAIR (C). All groups received a tibial arthroplasty using a Ti-6Al-4V implant. Groups B and C were infected per-operatively with a 5.5 log10 MRSA inoculum. After 1 week, groups C infected knees were surgically debrided. Groups A and C received 1 week of vancomycin. Pharmacokinetic profiles were obtained in group A following 1st and 5th injections. Animals were euthanized 2 weeks after the arthroplasty. Implants and tissue samples were processed for bacterial counts and histology.
Results:
Average vancomycin AUC0-12 h were 213.0 mg*h/L (1st injection) and 207.8 mg*h/L (5th injection), reaching clinical targets. All inoculated animals were infected. CFUs were reproducible in groups B. A sharp decrease in CFU was observed in groups C. Serum markers and leukocytes counts increased significantly in infected groups.
Conclusion:
We developed a reproducible rabbit model of PJI treated with DAIR, using vancomycin at clinically relevant concentrations.
Insights
A new rabbit model for prosthetic joint infection (PJI) was developed to test debridement, implant retention, and antibiotic therapy (DAIR). This model successfully demonstrated vancomycin
Area of Science:
- Orthopedic Surgery
- Infectious Diseases
- Pharmacology
Background:
- Prosthetic Joint Infection (PJI) is a severe complication following joint replacement surgery.
- The standard treatment for acute PJI, debridement, implant retention, and antibiotic therapy (DAIR), has a high failure rate, particularly in cases of Methicillin-resistant Staphylococcus aureus (MRSA) infections.
- There is a need for reliable animal models to study PJI and evaluate treatment efficacy.
Purpose of the Study:
- To develop and validate a reproducible rabbit model of prosthetic joint infection.
- To assess the efficacy of the DAIR strategy using vancomycin at clinically relevant dosages in this model.
- To evaluate vancomycin pharmacokinetics in the context of PJI treatment.
Main Methods:
- A tibial arthroplasty model was created in 15 rabbits using Ti-6Al-4V implants.
- Surgical knees were infected with MRSA. One week post-infection, the DAIR procedure was performed on infected knees.
- Vancomycin was administered for one week, and pharmacokinetic profiles were analyzed. Bacterial counts and histological analyses were performed on explanted implants and tissues.
Main Results:
- The rabbit model demonstrated reproducible MRSA infection and allowed for effective bacterial reduction following DAIR treatment.
- Vancomycin achieved pharmacokinetic profiles (AUC0-12h: 213.0 mg*h/L and 207.8 mg*h/L) that reached clinical targets.
- Infected groups showed significant increases in serum markers and leukocyte counts, indicating an inflammatory response.
Conclusions:
- A reproducible rabbit model for studying Prosthetic Joint Infection (PJI) treated with DAIR has been successfully developed.
- The study validates the use of vancomycin at clinically relevant concentrations within this model for PJI treatment.
- This model serves as a valuable tool for future research into PJI therapies.
