Development of an innovative in vivo model of PJI treated with DAIR

Abstract

IntroductionProsthetic 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 methodsA 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.ResultsAverage 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.ConclusionWe developed a reproducible rabbit model of PJI treated with DAIR, using vancomycin at clinically relevant concentrations.

2023 International Consensus Meeting on musculoskeletal infection: Summary from the treatment workgroup and consensus on treatment in preclinical models

“…Much has been published on PJI and DAIR models in rodents and rabbits. However, little information is available on DAIR models for other animals 8–12 . While there is no ideal model or one that very closely replicates clinical scenarios, moderate evidence supports that modest DAIR models exist.…”