Development of a piglet model of neonatal systemic Staphylococcus aureus infection

Abstract

Staphylococcus aureus (S. aureus) is a primary cause of death due to sepsis in neonatal intensive care units. Fatal sepsis is characterized by systemic inflammatory response syndrome (SIRS), leading to systemic inflammation and organ dysfunction. Herein, a clinically‐relevant piglet model of SIRS secondary to S. aureus infection was developed. Colostrum‐deprived pigs had umbilical catheters placed within 12h of birth and were fed sow's milk replacer formula. On d7, piglets were either non‐infected (n=2) or injected IV with 1ml/kg BW S. aureus (strain S54F9) at 103(low; n=3) or 105(high; n=3) CFU/ml. Blood was repeatedly sampled from the catheter to follow the course of cytokine response and piglets were euthanized 10–14d post‐infection. Most infected animals developed a transient fever (>;103.5°F) post‐infection. Infected animals had elevated WBC count and percentage of neutrophils, characteristic of SIRS. S. aureus was detected in the spleen (n=5), kidney (n=3), lung (n=3) and heart (n=2) of infected animals and high‐dose pigs developed rear limb septic arthritis confirmed by culture. Serum cytokine responses were variable; however, IL‐10 was highest in the first 24 h post‐infection, whereas IL‐6 peaked between 72–96 h post‐infection. In conclusion, we have established a piglet model of systemic S. aureus infection that can be used to investigate therapeutic nutritional interventions.