Non-Invasive Eradication of Biofilm on Metal Implants Using Alternating Magnetic Fields (AMF) and Antibiotics

Hundreds of thousands of human implant procedures require surgical revision each year due to infection. Infections are difficult to treat with conventional antibiotics due to the formation of biofilm on the implant surface. Our group is developing a non-invasive method to eliminate biofilm on metal implants using alternating magnetic fields (AMF), utilizing the physical principle of electromagnetic induction. The aims of this dissertation are to establish exposure parameters for biofilm elimination in the presence and absence of antibiotics, the development of treatment strategies, and investigation the mechanism of AMF towards biofilm. First, the elimination of biofilm on metal implant using intermittent alternating magnetic field (iAMF) and antibiotics was studied, showing iAMF and antibiotics are synergistic in their biofilm reducing capability. For Pseudomonas aeruginosa biofilm, bacterial burden was reduced > 3 log with iAMF and ciprofloxacin after 24 h compared with either treatment alone. This additional treatment effect was also found on Staphylococcus aureus. iAMF and antibiotic efficacy was seen across various iAMF settings, including different iAMF target temperatures, dose durations, and dosing intervals. Initial mechanistic studies revealed membrane disruption as one factor important for AMF enhanced antibacterial activity in the biofilm. Then, the impact factors generated by AMF, heat and electric current, to metal implants were studied separately. A mathematic model was built to describe the response of biofilm to heat based on Arrhenius equation in order to study the responses of various strains to heat. Also, the synergistic effect of heat and antibiotics was observed towards biofilm elimination at various treatment temperatures. Finally, the effect of alternating electric current was studied using a burst AMF (bAMF) strategy, in which negligible heating was produced. For Pseudomonas aeruginosa biofilm, bAMF was able to eliminate biofilm in combination with antibiotics for surface current densities ranging from 99 to 297 A/cm2. This effect was also observed with bAMF and linezolid or rifampin in Staphylococcus aureus but with higher surface current densities required to achieve the same level of biofilm reduction. The results of this study support the use of AMF to reduce biofilm on infected metal implants. The effect can be achieved through both thermal and electrical pathways, or a combination of both. When combined with antibiotics, the effect is amplified and can regularly achieve biofilm eradication. In the future, the results of this thesis can be used to define operating parameters for the non-invasive treatment of infected metal implants.