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Updated: Jul 7, 2026
Experimental Endocarditis Model of Methicillin Resistant Staphylococcus aureus (MRSA) in Rat
Published on: June 4, 2012
Development of a mouse model of induced Staphylococcus aureus infective endocarditis
Glenn W Gibson1, Steven C Kreuser, Janet M Riley
1Pfizer Global Research and Development, Groton, CT, USA. glenn.gibson@pfizer.com
Abstract:
We developed a mouse model of Staphylococcus aureus infective endocarditis to evaluate the efficacy of experimental antibacterial compounds for this disease. Experimental infective endocarditis was produced in CD1 mice by intravenous challenge with approximately 6 log10 colony-forming units (CFU) of methicillin-sensitive (MSSA) SA-3529 or -resistant (MRSA) SA-2015 S. aureus 1 d after aortic valve trauma. Valve trauma was produced by introduction of an indwelling 32-gauge polyurethane catheter into the aortic valve via the left carotid artery. Histologic examination of MSSA- and MRSA-infected and catheterized aortic valve sections revealed neutrophilic inflammation and vegetative bacterial colonies encapsulated within fibrin along the aortic valves 1 d after infection. The MSSA or MRSA endocarditis was determined to be catheter-dependent based on catheterized mice exhibiting heart bacterial counts 4 orders of magnitude greater than those seen for noncatheterized mice. The model was validated by using a 3-d regimen of vancomycin at exposures comparable to human dosing (500 microg x h/ml). Vancomycin treatment produced statistically significant reductions of 3.4 and 3.1 log10 CFU/heart for MSSA and MRSA, respectively, relative to controls. This mouse model of endocarditis shows promise in evaluating the predictive efficacy of antibiotics for S. aureus infective endocarditis.
Insights
Researchers developed a novel mouse model for Staphylococcus aureus infective endocarditis. This model effectively evaluates antibacterial compounds, demonstrating significant bacterial reduction with vancomycin treatment.
Area of Science:
- Microbiology
- Infectious Diseases
- Animal Models
Background:
- Staphylococcus aureus is a leading cause of infective endocarditis.
- Developing reliable models to test new antibacterial therapies is crucial.
Purpose of the Study:
- To establish and validate a mouse model for Staphylococcus aureus infective endocarditis.
- To assess the efficacy of experimental antibacterial compounds in this model.
Main Methods:
- Inducing infective endocarditis in CD1 mice via aortic valve trauma and subsequent intravenous challenge with MSSA or MRSA.
- Histological examination of aortic valves to confirm inflammation and bacterial colonization.
- Validating the model using a 3-day vancomycin treatment regimen at human-equivalent exposures.
Main Results:
- The developed model demonstrated catheter-dependent Staphylococcus aureus endocarditis.
- Histology confirmed neutrophilic inflammation and bacterial vegetations on aortic valves.
- Vancomycin treatment resulted in significant bacterial load reduction (3.4 and 3.1 log10 CFU/heart for MSSA and MRSA, respectively).
Conclusions:
- The established mouse model reliably mimics Staphylococcus aureus infective endocarditis.
- This model shows promise for predicting the efficacy of novel antibiotics against S. aureus endocarditis.
