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Is intracellular Staphylococcus aureus associated with recurrent infection in a rat model of open fracture?
Tao Gao1, Junqing Lin1, Changqing Zhang1
1Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Aims:
The purpose of this study was to determine whether intracellular Staphylococcus aureus is associated with recurrent infection in a rat model of open fracture.
Methods:
After stabilizing with Kirschner wire, we created a midshaft femur fracture in Sprague-Dawley rats and infected the wound with green fluorescent protein (GFP)-tagged S. aureus. After repeated debridement and negative swab culture was achieved, the isolation of GFP-containing cells from skin, bone marrow, and muscle was then performed. The composition and viability of intracellular S. aureus in isolated GFP-positive cells was assessed. We suppressed the host immune system and observed whether recurrent infection would occur. Finally, rats were assigned to one of six treatment groups (a combination of antibiotic treatment and implant removal/retention). The proportion of successful eradication was determined.
Results:
Green fluorescent protein-containing cells were successfully isolated after the swab culture was negative from skin (n = 0, 0%), muscle (n = 10, 100%), and bone marrow (n = 10, 100%) of a total of ten rats. The phagocytes were predominant in GFP-positive cells from muscle (73%) and bone marrow (81%) with a significantly higher viability of intracellular S. aureus (all p-values < 0.001). The recurrent infection occurred in up to 75% of rats after the immunosuppression. The proportion of successful eradication was not associated with implant retention or removal, and the efficacy of linezolid in eradicating intracellular S. aureus is significantly higher than that of vancomycin.
Conclusion:
Intracellular S. aureus is associated with recurrent infection in the rat model of open fracture. Usage of linezolid, a membrane-permeable antibiotic, is an effective strategy against intracellular S. aureus.Cite this article: Bone Joint Res. 2020;9(2):71-76.
Insights
Intracellular Staphylococcus aureus (S. aureus) contributes to recurrent open fracture infections in rats. Linezolid effectively eradicates intracellular S. aureus, unlike vancomycin.
Area of Science:
- Orthopedics
- Infectious Diseases
- Microbiology
Background:
- Recurrent Staphylococcus aureus infections pose a significant challenge in treating open fractures.
- The role of intracellular bacteria in persistent infections is an area of ongoing research.
Purpose of the Study:
- To investigate the association between intracellular Staphylococcus aureus and recurrent infections in a rat model of open fracture.
- To evaluate the efficacy of different treatment strategies against intracellular S. aureus.
Main Methods:
- A rat model of open femur fracture was established and infected with GFP-tagged S. aureus.
- Intracellular S. aureus within host cells was isolated and characterized after initial infection clearance.
- Rats were subjected to immunosuppression to assess recurrent infection rates and treated with antibiotics (linezolid, vancomycin) and/or implant management.
Main Results:
- Intracellular S. aureus was detected in muscle and bone marrow cells of infected rats, with high bacterial viability.
- Recurrent infections occurred in 75% of rats following immunosuppression.
- Linezolid demonstrated significantly higher efficacy in eradicating intracellular S. aureus compared to vancomycin.
Conclusions:
- Intracellular Staphylococcus aureus is implicated in the recurrence of open fracture infections.
- Linezolid, a membrane-permeable antibiotic, is a promising therapeutic option for targeting intracellular S. aureus infections.
