Novel treatment for bacterial sepsis - augmented passive immunotherapy

Antibacterial resistance is increasing and with the pipeline for new antibiotics drying up, novel therapeutic strategies are needed for the treatment of severe bacterial infections. One strategy that has shown much promise against Streptococcus pneumoniae infection is P4 peptide therapy (Bangert et al.,J. Infect. Dis. 2012, 205(9):1399–407). The administration of the P4 peptide results in the increased expression of Fcc receptors on phagocytic cells. When coupled with IVIG(pooled human IgG) this leads to a significant increase in opsonophagocytosis of the pathogen. In animal models of pneumococcal pneumonia, treatment with P4 peptide therapy resulted in increased survival during invasive pneumococcal pneumonia and prevention of the development of sepsis. IVIG is assumed to contain the entire panoply of anti-pathogen antibodies which, in theory, would make P4 therapy an immensely broad-spectrum therapeutic. This project goes on to look at the efficacy of P4 treatment against Gram-negative infections, namely E. coli and Klebsiella pneumoniae, as well as the pharmacokinetics and pharmacodynamics of P4 therapy.

Animal infection models will then be used to ascertain whether any enhancement in phagocytosis translates to improved survival during a disseminating E. coli peritonitis model.The P4 peptide has already shown much promise in the treatment of pneumococcal infections and has the potential to become an essential tool in the treatment of severe infections especially where a diagnosis has not yet been confirmed.