Induction of severe Staphylococcus aureus sepsis in pigs
© BioMed Central Ltd 2009
Published: 11 November 2009
Organ dysfunction is an integrated part of severe sepsis, and severe sepsis is one of the major causes of death in ICUs. Lately Gram-positive bacteria accounted for more than one-half of the overall sepsis cases reported in the USA, with Staphylococcus aureus being the most commonly isolated bacterium. Effective treatment of sepsis is still not optimal and good animal models are needed for research in pathogenesis and treatment. S. aureus infections are also common in pigs and are isolated from approximately 40% of embolic lesions found in slaughter-pigs.
To establish a porcine model of severe sepsis.
Twelve pigs in four groups were inoculated intravenously once or twice with 1 × 108 S. aureus/kg body weight and eutha-nized consecutively from 6 to 48 hours after inoculation. Mock-inoculated pigs served as controls. Body temperature was measured and blood samples were taken at regular intervals for bacteriology, haematology, clinical chemistry, and acute phase reactant determinations. Full necropsy was done and tissue samples were collected for bacteriology and histology. Apoptosis was measured in the spleen.
Onset of clinical disease (fever and lethargy) was seen at 7 to 8 hours after inoculation. Blood bacterial counts remained low throughout the study. SIRS characterized by fever, leukocytosis, increased levels of CRP, IL-6, IL-1β, TNFα, and decreased level of serum iron was detected after 12 hours. Both CRP and IL-6 levels peaked at 36 hours. Platelet numbers declined slightly and were lower than in the controls at 48 hours. Thromboelastography showed increased hypercoagulability over time. Levels of serum aspartate aminotransferase and bilirubin were elevated at 24 and 36 hours. Blood urea nitrogen levels had increased at 36 hours; however, no difference was seen in serum creatinine levels. Disseminated microabscesses were found in the lung at 6 hours, but had disappeared at 48 hours. In the bones, the presence of microabscesses progressed until 48 hours. Other histopatho-logical signs related to inoculation were limited to a renal microabscess at 12 hours, splenic microabscesses at 24 hours and centrilobular hepatic necrosis with thrombosis in one animal at 48 hours. In the liver and kidneys, various degrees of fibrinous exudation were found. The number of apoptotic cells in the splenic white pulp was increased at 48 hours.
All infected pigs developed sepsis with metastatic abscesses and at 48 hours severe sepsis was present with signs of dysfunction of the liver and the coagulation system. The splenic apoptotic response indicates reduced function and immuno-suppression.