IN VIVO EVALUATION OF THE EFFICACY OF LOCALLY DELIVERED ANTIBIOTICS ENCAPSULATED IN MICROPARTICLES FOR EARLY PJI: IMPROVING THE RESULTS OF DAIR

Objectives The purpose of the study was to evaluate the antimicrobial efficacy of rifampicin and ciprofloxacin loaded microparticles using a rabbit model of early prosthetic joint infection (PJI). Methods Previous approval of the local EC and following the declaration of Helsinki, an experimental study was conducted using an in vivo PJI model in New Zealand White rabbits. Preoperative data, including body temperature and weight were recorded. In the first phase, joint replacement surgery was performed with a 3D printed specie-specific implant, followed by inoculation of a biofilm forming strain of S. Aureus. During follow-up, clinical signs of infection (effusion, dehiscence, or fistula) were assessed. In the second phase, microbiological samples were collected and animals were assigned to two treatment groups: group A received surgical irrigation and debridement; group B received the same procedure plus local application of the antibiotic formulation to the prosthetic surface. Post-operative clinical, analytical and microbiological variables were recorded. In the final phase, animals were euthanized and blood and tissue samples were collected. Results Sixteen male New Zealand White rabbits were included in the study, with 8 animals allocated to each group. One subject from the control group was excluded due to death during the follow-up period. Both groups were comparable in terms of preoperative clinical parameters. During follow-up and prior to the second surgical procedure, 100% of the subjects in both groups exhibited clinical signs of infection. Microbiological cultures yielded pathogen isolation in all cases (100%), with no statistically significant differences in colony-forming unit (CFU) counts in either synovial fluid or tissue samples between the two groups (p = .39 and .42, respectively). Prior to the third surgical intervention, 85.7% (6/7) of the subjects in Group A showed clinical signs of infection, compared to 14.2% (1/8) in Group B. Microbiological cultures from both synovial fluid and tissue samples were positive in 85.7% (6/7) of Group A subjects and 14.2% (1/8) in Group B (p = .04). Biochemical analyses revealed statistically significant differences in liver enzyme levels (ALT [p=.02], AST [p=.03], and bilirubin [p.04]), higher in Group B, presumably associated with systemic rifampicin absorption, although without clinical relevance. Conclusions Although more studies are required, local delivery systems loaded with antibiotics may be a useful strategy to enhance the results of the debridement and implant retention strategies for the treatment of early PJI.