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A novel rat model of foreign body osteomyelitis for evaluation of antimicrobial efficacy
Cassandra L Brinkman1, Suzannah M Schmidt-Malan1, Melissa J Karau1
1Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, 55905, USA.
Abstract:
The most common organism-type causing orthopedic foreign body infection is the staphylococci, of which Staphylococcus aureus and Staphylococcus epidermidis are especially common. These organisms form biofilms on orthopedic foreign body surfaces, rendering such infections challenging and time consuming to treat. Our group evaluates novel therapeutics for orthopedic foreign body infection in animal models. A current limitation of most animal models is that that they only allow for the removal of one sample per animal, at the time of sacrifice. Herein, we describe a novel rat model of foreign body osteomyelitis that allows removal of foreign bodies at different time points, from the same infected animal. We demonstrate that this model can be used for both S. aureus and S. epidermidis orthopedic foreign body infection, with 3.56, 3.60 and 5.51 log10 cfu/cm2 S. aureus recovered at four, five and six weeks, respectively, after infection, and 2.08, 2.17 and 2.62 log10 cfu/cm2 S. epidermidis recovered at four, five and six weeks, respectively, after infection We evaluated the model with S. aureus infection treated with rifampin 25 mg/kg twice daily for 21 days. Using quantitative cultures, we were no longer able to detect bacteria as of the 14th day of treatment with bacteria becoming detectable again 7 days following die discontinuation of rifampin a period. This novel model allows monitoring of evolution of infection at the infection site in the same animal.
Insights
A new rat model allows repeated sampling from the same animal to study orthopedic foreign body infections caused by Staphylococcus aureus and Staphylococcus epidermidis. This model aids in evaluating new treatments for challenging biofilm infections.
Area of Science:
- Orthopedic Surgery
- Infectious Diseases
- Microbiology
- Animal Models
Background:
- Staphylococci, particularly Staphylococcus aureus and Staphylococcus epidermidis, are the primary causes of orthopedic foreign body infections.
- These bacteria form biofilms on implants, complicating treatment and necessitating effective therapeutic strategies.
- Existing animal models often limit data acquisition to a single sample per animal at sacrifice, hindering longitudinal study.
Purpose of the Study:
- To introduce and validate a novel rat model for studying orthopedic foreign body osteomyelitis.
- To enable serial collection of foreign bodies from the same infected animal at multiple time points.
- To assess the model's utility for both Staphylococcus aureus and Staphylococcus epidermidis infections and its response to antibiotic treatment.
Main Methods:
- Development of a rat model for foreign body osteomyelitis.
- Infection established with Staphylococcus aureus or Staphylococcus epidermidis.
- Serial removal of infected foreign bodies for quantitative culture at various time points post-infection and post-treatment.
Main Results:
- The model successfully supported both Staphylococcus aureus and Staphylococcus epidermidis orthopedic foreign body infections, with quantifiable bacterial loads over six weeks.
- Quantitative cultures showed increasing bacterial loads for both species over time (e.g., S. aureus: 3.56-5.51 log10 cfu/cm² from week 4 to 6).
- Treatment of Staphylococcus aureus infection with rifampin demonstrated bacterial clearance by day 14, with reappearance seven days after treatment cessation, highlighting treatment dynamics.
Conclusions:
- This novel rat model permits longitudinal monitoring of orthopedic foreign body infections within the same animal.
- It facilitates the evaluation of infection progression and therapeutic interventions for Staphylococcus aureus and Staphylococcus epidermidis.
- The model's ability to allow serial sampling provides a significant advantage over existing methods for studying these challenging infections.
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