ABSTRACT
Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes. Specifically, perturbation of HIF pathway and glycolysis genes by hypoxic preconditioning was associated with reduced leukocyte glucose utilisation, resulting in systemic rescue from a global negative energy state and myocardial protection. Thus we demonstrate that hypoxia preconditions the innate immune response and determines survival outcomes following bacterial infection through suppression of HIF-1α and neutrophil metabolism. The therapeutic implications of this work are that in the context of systemic or tissue hypoxia therapies that target the host response could improve infection associated morbidity and mortality.
ABSTRACT
This report describes a retrospective analysis of 33 patients admitted to an intensive care unit with suspicion of necrotising fasciitis (NF) of the extremities. The aim of the study was to clarify the clinical presentation of NF in order to determine when early surgery should be considered. Twenty-one patients with surgically confirmed NF were compared to 12 patients with superficial soft tissue infection. At admission, patients with NF were more likely to have skin areas of ischaemia or necrosis, fluid-filled vesicles, and severe sepsis or septic shock.
