My research interests and activities primarily focus on translational aspects of antimicrobial therapy of septic shock. In the past, I have also focused on a bench and bedside level at questions related to myocardial dysfunction in sepsis and septic shock. These latter studies continue with the co-operation of basic science investigators. More recent efforts have been focused basic and clinical aspects of pandemic (2009) H1N1 influenza infection.
As noted my primary interest is optimization of antimicrobial therapy in the context of septic shock. This question is being addressed in small animal and clinical studies. The basic premise of this work is that current antimicrobial therapy of septic shock is suboptimal in that it fails to recognize that a key determinant of outcome is rapidity of microbial clearance following onset of shock. In this theoretical model, the microbial biomass can be considered to be the central driving force in the development of septic shock. Based on an adaptation of Wigger’s hemorrhagic model of irreversible shock, there is only a limited period of time during which septic shock can be reversed without irreparable injury. This model of the disease process naturally leads to many testable hypotheses that span questions of molecular biology to clinical epidemiology.
In order to investigate these hypotheses, an integrated program of research from molecular biology through human and rodent cardiovascular pathophysiology to clinical epidemiology is being developed.
The primary tools for this effort are a small animal model of septic shock (both mouse and rat) and a newly developed clinical septic shock database drawn from multiple world-wide contributing sites which we have developed. This clinical database, currently encompassing >9000 individual patients, is by far the largest and most complete in existence.
Our theoretical model of septic shock implies that more rapid initiation of antimicrobial therapy after onset of hypotension should result in improved outcome. We have utilized our mouse and rat models of septic shock to confirm this hypothesis. Further, we have been able to retrospectively confirm these findings in our septic shock human dataset. We have further been able to demonstrate in our animal model (and obtain supportive evidence from our clinical database) that more effective antimicrobial killing in septic shock also yields improved outcome.
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