Prosthetic Joint Infection Research Models in NZW Rabbits: Opportunities for Standardization-A Systematic Review

Abstract

Prosthetic joint infection (PJI) is a major complication following total arthroplasty. Rising antimicrobial resistance (AMR) to antibiotics will further increase therapeutic insufficiency. New antibacterial technologies are being developed to prevent PJI. In vivo models are still needed to bridge the translational gap to clinical implementation. Though rabbit models have been used most frequently, there is no consensus about methodology and measured outcomes. The PubMed, Scopus, and EMBASE databases were searched for literature on PJI in rabbit models. Data extraction included bias control, experimental design, and outcome measures of the NZW rabbit models in the articles. A total of 60 articles were included in this systematic literature review. The articles were divided into six groups based on the PJI intervention: no intervention used (21%), revision surgery (14%), prevention with only antibiotics (21%), prevention with surface modifications (7%), prevention with coatings (23%), and others (14%). Despite the current availability of guidelines and recommendations regarding experimental design, bias control, and outcome measures, many articles neglect to report on these matters. Ultimately, this analysis aims to assist researchers in determining suitable clinically relevant methodologies and outcome measures for in vivo PJI models using NZW rabbits to test new antimicrobial technologies.

Keywords: ARRIVE guidelines; NZW rabbit; antibacterial technologies; in vivo; prosthetic joint infection.

Figure 1

PRISMA flow diagram of article selection. The database search resulted in a total of 575 studies. After duplicate removal and screening, 60 studies were left for data extraction.

Figure 2

Interventions used in the NZW rabbit PJI models in the articles included in this review. Articles studied no intervention/PJI model development (20%); antibiotics alone as prevention for PJI (20%); revision surgery as treatment for PJI (13%); surface modification of the implant as prevention for PJI (7%); coating on the implant as prevention for PJI (25%); or other interventions (15%). Created with Biorender.com (accessed on 14 May 2024).

Figure 3

Analysis of bias control Table 1, including: (a) blinding of the studies; (b) randomization of the studies.

Figure 4

Analysis of bias control Table 1, including (a) the sex of the rabbits included in the studies; (b) the age of the rabbits included in the studies; (c) the weight of the rabbits included in the studies; (d) caretaking of the rabbits included in this study, including if they could eat and drink ad libitum (a.l.), if they were provided with supplemental feeding when necessary, and if they were single housed or not.

Figure 5

Analysis of the experimental design of the articles included in this review, including: (a) the duration of the experiments from inoculation to euthanasia for studies that only investigated infection (left) and studies that investigated infection and osseointegration (right), and articles that studied multiple study durations were colored separately; (b) bacterial strains used in the studies; (c) the inoculum dose [absolute CFU] that was used to inoculate the rabbits; (d) the bone in which the implant was inserted; and (e) the way in which the inoculum was administered to the rabbit ([52,65,74,82,87,89]). Created with Biorender.com (accessed on 20 August 2024).