Despite a decade of efforts in engineering and clinical process improvement, medical device infections remain a leading cause of health care associated bloodstream infections and confer substantial morbidity, mortality, and cost. The microorganisms that contaminate engineered materials are ubiquitous, have evolved multiple redundant affinities for surfaces, and once adherent establish physical and metabolic safeguards to prevent their removal or killing. In 2013 these facts, in addition to the ever increasing fraction of the population harboring implanted devices, make it difficult to imagine a device-infection-free world. In this first competing renewal, we intend to pursue an important lead uncovered in our recent work, namely that the mechanical durability and antibiotic resistance of a biofilm can be significantly reduced by raising its temperature to levels safely used in other human medical applications. The overarching goal of this renewal is to study the thermal stability of medical biofilms in terms of soft matter properties relevant to dispersal and microbial viability in the presence of antibiotics. Our research question is straightforward and immediately clinically relevant: can modest increases in temperature be used in situ to soften biofilms and augment bacterial killing such that high- value devices can be salvaged that would otherwise require removal and replacement? Our aims thus are, (1) Establish for biofilms the mechanical and antibiotic response to supraphysiologic elevations in temperature, and determine the design parameters temperature needed to maximally reduce biofilm viability;(2) Using microrheology and light scattering methods, explore the mechanical implications of interactions between biofilm and host constituents, including interactions between bacterial polysaccharides and host proteins and bacterial nucleic acids with bacterial DNA binding proteins, and (3) Demonstrate in a rabbit model of central venous catheter infection the impact of temperature-based catheter salvage, including reduction in catheter biofilm burden and potential adverse consequences of treatment such as septic embolization of shed material and thermal injury to the catheter tunnel and jugular endothelium and intima.
Bloodstream infections are a common complication of implanted medical devices and are very difficult to treat without surgical removal of potentially life-sustaining devices. In this work, new strategies will be developed to degrade and remove bacterial communities that collect on medical devices during infection.
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