Standardized quantification of biofilm in a novel rabbit model of periprosthetic joint infection

Anabelle Visperas; Daniel Santana; Minseon Ju; Nathalie B Milbrandt; Yu Hsin Tsai; Sameera Wickramasinghe; Alison K Klika; Nicolas S Piuzzi; Anna Cristina S Samia; Carlos A Higuera-Rueda

doi:10.5194/jbji-7-91-2022

Standardized quantification of biofilm in a novel rabbit model of periprosthetic joint infection

J Bone Jt Infect. 2022 Apr 20;7(2):91-99. doi: 10.5194/jbji-7-91-2022. eCollection 2022.

Affiliations

¹ Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, OH, USA.
² Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA.
³ Department of Chemistry, Case Western Reserve University, Cleveland, OH, USA.
⁴ Department of Orthopaedic Surgery, Cleveland Clinic Florida, Weston, FL, USA.

Abstract

Periprosthetic joint infection (PJI) is one of the most devastating complications of total joint arthroplasty. The underlying pathogenesis involves the formation of bacterial biofilm that protects the pathogen from the host immune response and antibiotics, making eradication difficult. The aim of this study was to develop a rabbit model of knee PJI that would allow reliable biofilm quantification and permit the study of treatments for PJI. In this work, New Zealand white rabbits ( $n = 19$ ) underwent knee joint arthrotomy, titanium tibial implant insertion, and inoculation with Xen36 (bioluminescent Staphylococcus aureus) or a saline control after capsule closure. Biofilm was quantified via scanning electron microscopy (SEM) of the tibial explant 14 d after inoculation ( $n = 3$ noninfected, $n = 2$ infected). Rabbits underwent debridement, antibiotics, and implant retention (DAIR) ( $n = 6$ ) or sham surgery ( $n = 2$ noninfected, $n = 6$ infected) 14 d after inoculation, and they were sacrificed 14 d post-treatment. Tibial explant and periprosthetic tissues were examined for infection. Laboratory assays supported bacterial infection in infected animals. No differences in weight or C-reactive protein (CRP) were detected after DAIR compared to sham treatment. Biofilm coverage was significantly decreased with DAIR treatment when compared with sham treatment (61.4 % vs. 90.1 %, $p < 0$ .0011) and was absent in noninfected control explants. In summary, we have developed an experimental rabbit hemiarthroplasty knee PJI model with bacterial infection that reliably produces quantifiable biofilm and provides an opportunity to introduce treatments at 14 d. This model may be used to better understand the pathogenesis of this condition and to measure treatment strategies for PJI.