Development of a large animal rabbit model for chronic periprosthetic joint infection

Yagi, Haruyo; Kihara, Shinsuke; Mittwede, Peter N.; Maher, Patrick; Rothenberg, Adam C.; Falcione, Alyssa D C M; Chen, Antonia F.; Urish, Kenneth L.; Tuan, Rocky S.; Alexander, Peter G.

doi:10.1302/2046-3758.103.bjr-2019-0193.r3

Cited by 11 publications

(9 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, most models use non-clinically relevant implants, using either k-wires implanted in small rodents femurs – thus not exposed to the joint space or to the mechanical constraints usually applied to arthroplasty implants and inaccessible to a surgical debridement – ( 28 , 34 – 37 ), screws implanted in the lateral femoral condyles of rabbits – thus not exposed to mechanical stresses – ( 38 – 40 ), or the use of silicone elastomer implants replacing the proximal part of the tibia in rabbits but made of a material of no clinical relevance to PJI ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

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

Poilvache

Bambeke²

2022

Front. Med.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Poilvache

Bambeke²

2022

Front. Med.

View full text Add to dashboard Cite

show abstract

“…Oftentimes, bacteria protected by biofilms can multiply their resistance to antibiotics upwards of 1000 times. Failure to address the biofilm ensures recurrence of infection in short order, highlighting the importance of proper debridement [38][39][40][41][42].…”

Section: Role Of Intra-articular Irrigationmentioning

confidence: 99%

A review of current practices in periprosthetic joint infection debridement and revision arthroplasty

et al. 2022

View full text Add to dashboard Cite

Background Periprosthetic joint infection remains a significant challenge for arthroplasty surgeons globally. Over the last few decades, there has been much advancement in terms of treatment and diagnosis, however, the fight rages on. As management of periprosthetic joint infections continues to evolve, it is critical to reflect back on current debridement practices to establish common ground as well as identify areas for future research and improvement. Body In order to understand the debridement techniques of periprosthetic joint infections, one must also understand how to diagnose a periprosthetic joint infection. Multiple definitions have been elucidated over the years with no single consensus established but rather sets of criteria. Once a diagnosis has been established the decision of debridement method becomes whether to proceed with single vs two-stage revision based on the probability of infection as well as individual patient factors. After much study, two-stage revision has emerged as the gold standard in the management of periprosthetic infections but single-stage remains prominent with further and further research. Conclusion Despite decades of data, there is no single treatment algorithm for periprosthetic joint infections and subsequent debridement technique. Our review touches on the goals of debridement while providing a perspective as to diagnosis and the particulars of how intraoperative factors such as intraarticular irrigation can play pivotal roles in infection eradication. By providing a perspective on current debridement practices, we hope to encourage future study and debate on how to address periprosthetic joint infections best.

show abstract

“…Rabbit PJI surgical models were performed according to Yagi et al (2021) [22]. Rabbits were anesthetized with 20 mg/kg ketamine, 2 mg/kg xylazine, and 1-3% isoflurane inhalation.…”

Section: Pji Rabbit Surgical Modelsmentioning

confidence: 99%

Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class

Huang¹,

Brothers

Mandell

et al. 2022

PLoS ONE

Self Cite

View full text Add to dashboard Cite

The absence of novel antibiotics for drug-resistant and biofilm-associated infections is a global public health crisis. Antimicrobial peptides explored to address this need have encountered significant development challenges associated with size, toxicity, safety profile, and pharmacokinetics. We designed PLG0206, an engineered antimicrobial peptide, to address these limitations. PLG0206 has broad-spectrum activity against >1,200 multidrugresistant (MDR) ESKAPEE clinical isolates, is rapidly bactericidal, and displays potent antibiofilm activity against diverse MDR pathogens. PLG0206 displays activity in diverse animal infection models following both systemic (urinary tract infection) and local (prosthetic joint infection) administration. These findings support continuing clinical development of PLG0206 and validate use of rational design for peptide therapeutics to overcome limitations associated with difficult-to-drug pharmaceutical targets.

show abstract

Development of a large animal rabbit model for chronic periprosthetic joint infection

Cited by 11 publications

References 50 publications

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

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

A review of current practices in periprosthetic joint infection debridement and revision arthroplasty

Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class

Contact Info

Product

Resources

About