Biofilm bacteria are estimated to cause two thirds of infections in modern clinical practice. In biofilms, microorganisms are protected from killing by innate host defenses and most available antimicrobial agents, culminating in the need for device removal in many device-associated infections (e.g., prosthetic joint infection). Given the failure of antimicrobics in the management of biofilm-associated device infections, a novel and innovative therapeutic and preventive non-antimicrobial approach is needed. Such a strategy would limit emergence of conventional antimicrobial resistance, as conventional antimicrobial agents would not be needed. Such a strategy would also limit toxicity associated with systemic antimicrobial agents. The preliminary in vitro studies described in our first submission demonstrated that electrical currents of 20 to 2000
Microorganisms in biofilms cause a wide range of human infections, and biofilm microorganisms are resistant to most antibiotics used in clinical practice. {We have shown that electrical current is active against biofilms of six types of bacteria and one type of yeast in the laboratory and against one type of bacteria in an animal model.} We hypothesize that electrical current is active against a variety of bacteria and fungi in biofilms, which we plan to test in the laboratory and in an animal model. We further hypothesize that electrical current will not only treat, but will also prevent biofilm formation, which we will also test in the laboratory and in an animal model. We will examine the mechanism of the observed effect. We will establish optimal parameters to maximize the activity of electrical current against microbial biofilms. {And finally, we will characterize adverse effects associated with delivery of electrical current using our animal model.} Results of this study will provide a rationale and supporting data for use of electrical current for prevention and treatment of implant-associated infections (especially bone and joint infections) in humans. This new strategy would overcome the resistance to traditional antibiotics of microorganisms in biofilms.Public Health Relevance
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