Preclinical models of vertebral osteomyelitis and associated infections: Current models and recommendations for study design

Abstract

Spine-related infections, such as vertebral osteomyelitis, discitis, or spondylitis, are rare diseases that mostly affect adults, and are usually of hematogenous origin. The incidence of this condition has gradually risen in recent years because of increases in spine-related surgery and hospital-acquired infections, an aging population, and intravenous (IV) drug use. Spine infections are most commonly caused by Staphylococcus aureus, while other systemic infections such as tuberculosis and brucellosis can also cause spondylitis. Various animal models of vertebral osteomyelitis and associated infections have been investigated in mouse, rat, chicken, rabbit, dog, and sheep models by hematogenous and direct inoculation in surgery, each with their strengths and limitations. This review is the first of its kind to concisely analyze the various existing animal models used to reproduce clinically relevant models of infection. Spine-related infection models must address the unique anatomy of the spine, the avascular nature of its structures and tissues and the consequences of tissue destruction such as spinal cord compression. Further investigation is necessary to elucidate the specific mechanisms of host-microbe response to inform antimicrobial therapy and administration techniques in a technically demanding body cavity. Small-animal models are not suitable for large instrumentation, and difficult IV access thwarts antibiotic administration. In contrast, large-animal models can be implanted with clinically relevant instrumentation and are resilient to repeat procedures to study postoperative infection. A canine model of infection offers a unique opportunity to design and investigate antimicrobial treatments through recruitment a rich population of canine patients, presenting with a natural disease that is suitable for randomized trials.

The First Case of Infectious Spondylitis Caused by Gemella bergeri

“…Infectious spondylitis accounts for approximately 3–5% of all osteomyelitis cases yearly, and its incidence has increased in recent years. Infectious spondylitis often presents as a non-specific clinical condition; therefore, its diagnosis is often delayed [ 14 , 15 ]. Infectious spondylitis can usually occur through the following routes: hematogenous spread from a distant site or focus of infection, direct inoculation, or contiguous spread from adjacent soft tissue infection [ 15 ].…”

Doxycycline as a Potential MMP-1 Inhibitor for the Treatment of Spondylitis Tuberculosis: A Study in Rabbit Model

“…Ketoprofen was administered intramuscularly at 3 mg/kg BW every 12 hours for 3 days. The principles of standard precautions, established safety measures, aseptic technique, and animal ethics were upheld in implementing this surgical protocol [32,33].…”

Controversies in spine research: Organ culture versus in vivo models for studies of the intervertebral disc

“…In doing so we also identify their respective limitations, and the continued need to strive for improved experimental platforms in order to achieve the best possible treatment outcomes for LBP patients. Many reviews of different IVD model systems are available in the published literature, 23 , 93 , 168 , 169 , 170 , 171 and these can serve as valuable resources for researchers seeking the best model system for their research question. Consideration should also be given to the development and use of standardized outcome measures for various models, 172 , 173 which makes comparing results across studies easier and more valuable.…”