Development of a mouse model of induced Staphylococcus aureus infective endocarditis.
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.
Gibson
Glenn W
GW
Pfizer Global Research and Development, Groton, CT, USA. glenn.gibson@pfizer.com
Kreuser
Steven C
SC
Riley
Janet M
JM
Rosebury-Smith
Wendy S
WS
Courtney
Cynthia L
CL
Juneau
Paul L
PL
Hollembaek
John M
JM
Zhu
Tong
T
Huband
Michael D
MD
Brammer
David W
DW
Brieland
Joan K
JK
Sulavik
Mark C
MC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D001021:Aortic Valve / Q000382:microbiology / Q000473:pathology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology; D005260:Female; D016106:Methicillin Resistance; D051379:Mice; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D014640:Vancomycin / Q000008:administration & dosage / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D014640:Vancomycin