| Objective:Resistant Staphylococcus aureus (MRSA)infective endocarditis (IE) is a serious threat to human life. Even in the case of drug therapy, there is still a high rate of mortality. The rodent model of catheter-induced endocarditis, resembling human disease, is more conductive to the study of pathogenic mechanism of bacteria and evaluation of the efficacy of new antimicrobial agents.Methods:1. Establishment of rodent model of catheter-induced endocarditis1.1 Rat model of infective endocarditis:A PE-10 catheter was inserted through the carotid artery into the aortic valve to establish the rat model of endocarditis. S.aureus strain ATCC43300 was injected through the tail vein and the inoculum was 103,104 and 105CFU/animal respectively. Rats were sacrificed 1,3,5 and 7 days post-infection respectively. Aortic valve vegetations, kidneys and spleens were removed and bacterial burden were examined by quantitative culture. Comprehensive evaluation model is established successfully.1.2 Mouse model of infective endocarditis:A PE-01 catheter was inserted into the carotid artery of mouse to establish the mouse model of endocarditis by stereo microscope. S.aureus strain ATCC43300 was injected through the tail vein and the inoculum was 103,104,105 and 106CFU/animal respectively. Mice were sacrificed 1,2 and 3 days post-infection. Aortic valve vegetations, kidneys and spleens were removed and bacterial burden were examined by quantitative culture. Comprehensive evaluation model is established successfully.2. Evaluation the efficacy of antibioticsTherapeutic effect of antibiotic frequently used in the clinical to treat S.aureus infections were evaluated by rat endocarditis model established in this study. Rats were received either vancomycin (40mg/kg, twice daily), teicoplanin (15mg/kg, twice daily after a loading dose of 30mg/kg), or daptomycin (40mg/kg, once daily). Control group were given the same volume of normal saline.Result:1. 1d after infection, heart catheterization rats developed vegetations on the aortic valve, and vegetations in the ventricle wall were found in serveral rats with serious MRSA infectious. The bacterial burden of IE in the rats were increasing along with the increase of inoculum and days of infection. IE was the most serious after 3 days infection, within 5-7days after infection, the bacterial burden and vegetation weight were various among different inoculum doses. The bacterial burden in spleen and kidney has the same trend with heart, but the number were not as high as the vegetations. There was no vegetation in non surgical infection group and non infection group.2. A few vegetations on mice heart valve were seen in non surgical infection group. 1d after infection, the bacterial burden in mice aortic valve vegetations increased along with bacteria concentration. As the infection time increasing, there is no correlation between infection and IE. The inoculum of 103～106CFU/animal were successful to form MRSA IE of mouse.3. Compared with the control group, the vegetation weight of mice treated with vancomycin and daptomycin decreased significantly; The bacterial burden of vegetations in vancomycin group and teicoplanin group decreased significantly.Conclusion:1. In this study we successfully established rat and mouse model of infective endocarditis, cardiac valve developed a great number of vegetations.2. Vancomycin was effective in rat infective endocarditis; teicoplanin was able to reduce the bacterial burden in vegetations, but had no effect on vegetation weight; Mice given daptomycin had lower vegetation weight, but there is no significant difference on bacterial burden in vegetation compared with the control group.3. The rodent model of infective endocarditis establishment in this study are suitable for preclinical pharmacodynamics research and drug efficacy evaluation. |
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