@article {demourdant_novel_2023,
	title = {A novel rodent model of chronic spinal implant-associated infection},
	journal = {The Spine Journal: Official Journal of the North American Spine Society},
	volume = {23},
	number = {9},
	year = {2023},
	month = {sep},
	pages = {1389{\textendash}1399},
	abstract = {BACKGROUND CONTEXT: Bacterial infection of spinal instrumentation is a significant challenge in spinal fusion surgery. Although the intraoperative local application of powdered vancomycin is common practice for mitigating infection, the antimicrobial effects of this route of administration are short-lived. Therefore, novel antibiotic-loaded bone grafts as well as a reliable animal model to permit the testing of such therapies are needed to improve the efficacy of infection reduction practices in spinal fusion surgery. PURPOSE: This study aims~to establish a clinically relevant rat model of spinal implant-associated infection to permit the evaluation of antimicrobial bone graft materials used in spinal fusion. STUDY DESIGN: Rodent study of chronic spinal implant-associated infection. METHODS: Instrumentation anchored in and spanning the vertebral bodies of L4 and L5 was inoculated with bioluminescent methicillin-resistant Staphylococcus aureus bacteria (MRSA). Infection was monitored using an in vivo imaging system (IVIS) for 8 weeks. Spines were harvested and evaluated histologically, and colony-forming units (CFUs) were quantified in harvested implants and spinal tissue. RESULTS: Postsurgical analysis of bacterial infection in vivo demonstrated stratification between MRSA and phosphate-buffered saline (PBS) control groups during the first 4 weeks of the 8-week infection period, indicating the successful establishment of acute infection. Over the 8-week chronic infection period, groups inoculated with 1~{\texttimes}~105 MRSA CFU and 1~{\texttimes}~106 MRSA CFU demonstrated significantly higher bioluminescence than groups inoculated with PBS control (p~=~0.009 and p~=~0.041 respectively). Histological examination at 8 weeks postimplantation revealed the presence of abscesses localized to implant placement in all MRSA inoculation groups, with the most pervasive abscess formation in samples inoculated with 1~{\texttimes}~105 MRSA CFU and 1~{\texttimes}~106 MRSA CFU. Quantification of CFU plated from harvested spinal tissue at 8 weeks post-implantation revealed the 1~{\texttimes}~105 MRSA CFU inoculation group as the only group with a significantly greater average CFU count compared to PBS control (p~=~0.017). Further, CFU quantification from harvested spinal tissue was greater than CFU quantification from harvested implants across all inoculation groups. CONCLUSION: Our model demonstrated that the inoculation dosage of 1~{\texttimes}~105 MRSA CFU exhibited the most robust chronic infection within instrumented vertebral bodies. This dosage had the greatest difference in bioluminescence signal from control (p < 0.01), the lowest mortality (0\% compared to 50\% for samples inoculated with 1~{\texttimes}~106 MRSA CFU), and a significantly higher amount of CFUs from harvested spine samples than CFUs from control harvested spine samples. Further, histological analysis confirmed the reliability of this novel rodent model of implanted-associated infection to establish infection and biofilm formation of MRSA for all inoculation groups. CLINICAL SIGNIFICANCE: This model is intended to simulate the infection of instrumentation used in spinal fusion surgeries concerning implant locality and material. This model may evaluate potential antimicrobial and osteogenic biomaterials and investigate the relationship between implant-associated infection and failed fusion.},
	keywords = {animal, Animals, Anti-Bacterial Agents, Disease Models, Implant-associated infection, Methicillin-Resistant Staphylococcus aureus, Osteomyelitis, persistent infection, Prosthesis-Related Infections, Rats, Reproducibility of Results, Rodent model, Rodentia, Spinal arthrodesis, Spinal instrumentation, Spine infection, Staphylococcal Infections},
	issn = {1878-1632},
	doi = {10.1016/j.spinee.2023.05.014},
	author = {DeMourdant, Trevor and Rajkovic, Christian J. and Tracz, Jovanna A. and Perdomo-Pantoja, Alexander and Judy, Brendan F. and Hernandez, Vaughn N. and Lin, Jessica and Lazzari, Julianna L. and Dikeman, Dustin A. and Archer, Nathan K. and Davis, Kimberly M. and Gordon, Oren and Witham, Timothy F.}
}
