Bacterial biofilm infections on medical implants are extremely difficult to eliminate using conventional antibiotic therapy. In vitro experiments in our lab have shown that the application of low frequency, low intensity ultrasound can enhance the action of antibiotics sufficiently that the viability of biofilms can be reduced orders of magnitude in short term exposure (2 hrs.), and can be reduced to zero viability after 6 hrs. of treatment for the particular system examine. This research proposal is focused on developing an animal test to determine whether this enhancement of antibiotic action will also occur in vivo. Specifically the research will develop a simple infection model in a rabbit by inserting 2 biofilm-contaminated polymeric disks subcutaneously in the back of the rabbit. The animal will be given systemic antibiotics, and one of the infected implants will be exposed to ultrasound of various frequencies, powers, and durations. Both implants will be recovered and the viable bacteria on the implants will be determined and compared. Several experimental parameters will be studied to determine 1) if the enhanced killing can be reproduced in an animal model, and 2) what the optimal parameters are for quickly treating the implant infections. The variables will be ultrasonic frequency (47 and 500 kHz), ultrasonic power density (1.0 and 0.1 W.cm2), duration of ultrasonic exposure (6, 12, 24, and 48 hrs.), age of infection (24 and 48 hrs.), bacterial species (E. coli and P. aeruginosa), antibiotic (gentamicin and enrofloxacin), and implant material (polyethylene and silicone rubber). In addition, the effect of long term exposure (24 and 48 hrs.) of ultrasound on non-infected rabbit tissue will be assessed. Experiments will also look for signs of spread of the infection by examining tissues taken from the implant site, lungs, liver and kidney. The most significant results of this research will be to know whether the ultrasonically enhanced antibiotic action against biofilms observed in vitro can be extended to living animals. If this is the case, this therapy has potential to relieve the pain and eliminate the need for replacement surgery for thousands of people who have implant infections.
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