A “Two-Hit” Model of Sepsis

A “Two-Hit” Model of Sepsis

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TransPharm recently validated a “two-hit” model of sepsis in which mice undergo cecal ligation and puncture (CLP) followed by intranasal instillation with bacteria to initiate a pulmonary infection.

Although sepsis is a major cause of mortality in hospital patients, death often results from the synergistic effect of a concurrent nosocomial infection rather than the initial septic event on its own. Data indicates that primary sublethal sepsis weakens the immune system and increases susceptibility to secondary infection and death. Our two-hit model is clinically relevant as it reflects the increased yet delayed mortality from a secondary infection, such as pneumonia, after sepsis. Further, the extended duration of infection allows for the evaluation of therapeutics targeting specific stages of the immune response.

TransPharm has validated the “two-hit” model using Pseudomonas aeruginosa, although published literature has also demonstrated this effect with Staphylococcus aureus and Streptococcus pneumoniae. Validations with these and other pathogens are available upon request. Contact us to request additional information or a free, no-obligation quote.


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