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In situ treatment strategies for medical device associated infections

What we study: The underlying pathobiology of medical device associate infection is related to biofilm formation on device surfaces. Biofilms are communities of sessile bacteria enclosed within an extracellular matrix which offers constituent bacteria protection from antibiotics and host response. While microbiologists consider biofilms from a purely biological perspective, we view biofilms as soft matter or complex fluids. This allows us to consider and develop novel physical treatments (e.g., thermal and mechanical) in conjunction with traditional chemical and biological treatments.

Why it matters: While preventive strategies reduce, they cannot eliminate bacterial adhesion and colonization of implanted medical devices over time. Current in situ treatment strategies fail to overcome the physical and metabolic defenses afforded by microbial biofilms, which ultimately disseminate to the bloodstream and distal sites. As a consequence of this resilience and risk of metastasis, surgical removal remains the most effective treatment but adds significant morbidity, mortality, and cost. This motivates the search for in situ anti-biofilm strategies.

 

Our key contributions: We have shown that biofilms can be interrogated as soft matter or complex fluids that respond to thermal, mechanical, or chemical treatments. We have developed in vitro biofilm models that incorporate human blood proteins that more closely mimic in vivo conditions and used those models to further understanding of host-pathogen interactions with respect to abiotic substrates. Finally, we demonstrated that bacteria on the device surface respond differently to treatments than bacteria that has been disseminated or debrided from that surface. This is critical in that a biofilm treatment that leaves disseminated material viable is spreading, not eradicating the infection. This work forms the basis of an R01 to develop a strategy using thermal and mechanical treatments for central-line associated bloodstream infections.

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