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INTRODUCTION: Antimicrobial resistance threatens to undermine treatment of severe infection; new therapeutic strategies are urgently needed. Preclinical work shows that augmented passive immunotherapy with P4 peptide increases phagocytic activity and shows promise as a novel therapeutic strategy. Our aim was to determine ex vivo P4 activity in a target population of patients admitted to critical care with severe infection. METHODS: We prospectively recruited UK critical care unit patients with severe sepsis and observed clinical course (≥3 months postdischarge). Blood samples were taken in early (≤48 h postdiagnosis, n = 54), latent (7 days postdiagnosis, n = 39), and convalescent (3-6 months postdiagnosis, n = 18) phases of disease. The primary outcome measure was killing of opsonized Streptococcus pneumoniae by neutrophils with and without P4 peptide stimulation. We also used a flow cytometric whole blood phagocytosis assay to determine phagocyte association and oxidation of intraphagosomal reporter beads. RESULTS: P4 peptide increased neutrophil killing of opsonized pneumococci by 8.6% (confidence interval 6.35-10.76, P 

Original publication




Journal article



Publication Date





635 - 641


Aged, Female, Flow Cytometry, Humans, Immunization, Passive, Male, Middle Aged, Neutrophils, Oligopeptides, Phagocytes, Phagocytosis, Prospective Studies, Sepsis, Streptococcus pneumoniae