Bacteria growing in biofilms cause a wide range of human infections. Biofilm bacteria are resistant to antimicrobials at levels 500 to 5,000 times higher than those needed to kill non-biofilm bacteria. In vitro experiments have shown that electric current can enhance the activity of aminoglycosides, quinolones or oxytetracycline against bacteria in biofilms; this has been termed the 'bioelectric effect.' The purpose of this exploratory research is to determine whether the in vitro bioelectric effect is generalizable across antimicrobial class, and to perform preliminary studies to determine whether there is an in vivo bioelectric effect. Two Specific Aims are proposed. Specific Aim 1. It will be determined whether the in vitro application of electric current can enhance the killing of biofilm bacteria by non-aminoglycoside, non-quinolone, non-tetracycline antimicrobics and whether the bioelectric effect is generalizable to Staphylococcus aureus. An in vitro model incorporating biophotonic imaging will be used wherein electricity will be passed through S. aureus, Staphylococcus epidermidis, or Pseudomonas aeruginosa biofilms exposed to antimicrobials in use in clinical practice and representing a variety of antimicrobial mechanisms of action. Specific Aim 2. It will be determined whether the enhancement of antimicrobic killing of biofilm-associated bacteria will occur in a living animal. An animal model of foreign body osteomyelitis will be developed wherein wires will be inserted into the tibiae of rabbits and then contaminated with S. epidermidis. Four weeks later, the animals will be given a systemic antimicrobial and/or the infected wires will be exposed to direct electrical current. Bacteria on the wires and in the surrounding bone will be quantified using culture and biophotonic imaging. The most significant results of this research will be to know whether the electrically enhanced action of aminoglycoside, quinolone, or tetracycline antimicrobics observed in vitro against bacterial biofilms is active using antimicrobial agents representing other antimicrobial classes and is active in an animal model of biofilm-mediated infection. Results of these exploratory studies are expected to provide a rationale and preliminary data for the use of the bioelectric effect in humans for the prevention and treatment of device- related bacterial infections. Direct electrical current has already been safely used in humans for fracture healing. Application of direct electric current with antimicrobial chemotherapy in humans has the potential to eliminate the need for device removal in human device-related infections. This novel but simple resistance reversing strategy may generalize to a wide variety of antimicrobics and microorganisms and a wide variety of biofilm-associated human infections. [unreadable] [unreadable] [unreadable] [unreadable]