Ultrasonic Enhancement of Antibiotic Action on Escherichia coli Biofilms: an In Vivo Model

Abstract

Biofilm infections are a common complication of prosthetic devices in humans. Previous in vitro research has determined that low-frequency ultrasound combined with aminoglycoside antibiotics is an effective method of killing biofilms. We report the development of an in vivo model to determine if ultrasound enhances antibiotic action. Two 24-h-old Escherichia coli (ATCC 10798) biofilms grown on polyethylene disks were implanted subcutaneously on the backs of New Zealand White female rabbits, one on each side of the spine. Low-frequency (28.48-kHz) and low-power-density (100- and 300-mW/cm2) continuous ultrasound treatment was applied for 24 h with and without systemic administration of gentamicin. The disks were then removed, and the number of viable bacteria on each disk was determined. At the low ultrasonic power used in this study, exposure to ultrasound only (no gentamicin) caused no significant difference in bacterial viability. In the presence of antibiotic, there was a significant reduction due to 300-mW/cm2 ultrasound (P = 0.0485) but no significant reduction due to 100-mW/cm2 ultrasound. Tissue damage to the skin was noted at the 300-mW/cm2 treatment level. Further development of this technique has promise in treatment of clinical implant infections.

Advances in ureteral stent technology

“…In vivo applications of this bioelectric process, termed``iontophoresis'', still have to be developed, but the process may be utilized for sterilization of tubing and instruments which can harbor bio®lms [48,67,68,70]. Finally, low-intensity ultrasound (500 kHz and 10 mW/cm 2 ) may alter bio®lms, and enhance the ecacy of drugs such as gentamicin on Pseudomonas aeruginosa [57].…”

Microbial Colonization of Medical Devices and Novel Preventive Strategies

“…Whereas exposure to ultrasound alone caused no consi-derable difference in bacterial viability, in the presence of gentamicin, there was a substantial reduction in bacterial viability (the bioacoustic effect). Here, the ultrasound significantly reduced bacterial viability below that of nontreated biofilms without damage to the skin [67,68]. They hypothesized that stable cavitation or sonoporation might be involved in increasing the transport of antibiotics into the bacteria either by reducing the mass transfer boundary layer around the cells, or by altering the cell membrane, thus allowing the antibiotics to diffuse through newly formed membrane pores.…”

“…Carmen et al [66] reported that S. epidermidis biofilms responded favorably to combinations of ultrasound and vancomycin at 48 hours of insonation. In addition, pulsed ultrasound enhances the killing of E. coli biofilms by aminoglycosides in a rabbit model with subcutaneously implanted polyethylene disks [67,68]. These authors applied low-frequency (28.48 kHz) and low-power density (300 mWcm -2 ) ultrasound treatment for 24 hours with and without systemic administration of gentamicin.…”

Ultrasound-induced cavitation: applications in drug and gene delivery

“…A large body of in vitro and in vivo literature exists on enhanced uptake of unbound chemicals into mammalian cells [152,153], and, especially tumour cells [154][155][156][157][158], in the presence of ultrasound. Similarly, ultrasound potentiates the effect of antibiotics on bacteria in culture [159][160][161] and in animals [162,163]. Ultrasound has also been used for selective delivery of conjugated drugs to their targets, avoiding the harmful side effects.…”