Poilvache Hervé, Van Bambeke Françoise, Cornu Olivier
Neuro Musculo-Skeletal Laboratory, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium.
Cellular and Molecular Pharmacology Laboratory, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
Front Med (Lausanne). 2022 Oct 13;9:984814. doi: 10.3389/fmed.2022.984814. eCollection 2022.
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.
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.
Average vancomycin AUC were 213.0 mgh/L (1st injection) and 207.8 mgh/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.
We developed a reproducible rabbit model of PJI treated with DAIR, using vancomycin at clinically relevant concentrations.
人工关节感染(PJI)是关节置换的灾难性并发症。清创、保留植入物和抗生素治疗(DAIR)是急性感染的常用策略,但在45%的耐甲氧西林金黄色葡萄球菌(MRSA)感染中失败。我们描述了一种兔感染性关节成形术模型的建立,该模型采用清创术和具有临床相关剂量的万古霉素疗程进行治疗。
总共15只兔子被分为三组:万古霉素药代动力学组(A)、感染组(B)和DAIR组(C)。所有组均使用Ti-6Al-4V植入物进行胫骨关节成形术。B组和C组在手术中接种5.5 log10的MRSA接种物。1周后,对C组感染的膝关节进行手术清创。A组和C组接受1周的万古霉素治疗。在第一次和第五次注射后,在A组中获得药代动力学曲线。在关节成形术后2周对动物实施安乐死。对植入物和组织样本进行细菌计数和组织学处理。
万古霉素的平均曲线下面积(AUC)在第一次注射时为213.0 mgh/L,在第五次注射时为207.8 mgh/L,达到临床目标。所有接种动物均被感染。B组的菌落形成单位(CFU)具有可重复性。C组的CFU明显下降。感染组的血清标志物和白细胞计数显著增加。
我们使用临床相关浓度的万古霉素,建立了一种经DAIR治疗的可重复的兔PJI模型。