Ultrasonically Enhanced Vancomycin Activity Against Staphylococcus Epidermidis Biofilms in Vivo

Abstract

SUMMARYInfection of implanted medical devices by Gram-positive organisms such as Staphylococcus ssp. is a serious concern in the biomaterial community. In this research the application of low frequency ultrasound to enhance the activity of vancomycin against implanted Staphylococcus epidermidis biofilms was examined. Polyethylene disks covered with a biofilm of S. epidermidis were implanted subcutaneously in rabbits on both sides of their spine. The rabbits received systemic vancomycin for the duration of the experiment. Following 24 h of recovery, one disk was insonated for 24 or 48 h while the other was a control. Disks were removed and viable bacteria counted. At 24 h of insonation, there was no difference in viable counts between control and insonated biofilms, while at 48 h of insonation there were statistically fewer viable bacteria in the insonated biofilm. The S. epidermidis biofilms responded favorably to combinations of ultrasound and vancomycin, but longer treatment times are required for this Gram-positive organism than was observed previously for a Gram-negative species.

Effect of Delayed Pulsed-Wave Ultrasound on Local Pharmacokinetics and Pharmacodynamics of Vancomycin-Loaded Acrylic Bone Cement In Vivo

“…Pitt and coworkers (1,2,16,17,18) found antibacterial synergism between antibiotics and ultrasound, or the bioacoustic effect. This effect was attributed to a sonoporation-induced inflow of the antibiotic through a membrane.…”

“…We defined the enhanced reduction as the difference in bacterial density between CG samples and samples from either UG 0-12 or UG [12][13][14][15][16][17][18][19][20][21][22][23][24] . This reduction signified the enhanced antimicrobial efficacy of cement produced by ultrasound (1). Isolates from all positive cultures were identified by colony morphologies, Gram staining, and catalase and coagulase tests (24).…”

Prevention and treatment of biofilms by hybrid- and nanotechnologies

“…56 Ultrasonic energy can also release drugs from delivery devices (drug release by passive diffusion resulting in rapid dissipation to sublethal concentrations) in a triggered manner, increase cell membrane permeability, enhance microconvection by heating, and stimulate active or passive uptake of the antibiotics, thereby causing cavitation and disruption of cell membranes and biofilm. [56][57][58][59] These properties have been leveraged against various in vitro pathogenic models of S. epidermidis, P. aeruginosa, and E. coli, [60][61][62] and in vivo killing of E. coli biofilms on subcutaneous polyethylene discs containing gentamicin and vancomycin in rabbit models. 60,61,63 Interestingly, similar to EC, low-frequency US (70 kHz) with low acoustic intensity increased the transport of oxygen and nutrients to the cells, thereby killing S. epidermidis, P. aeruginosa, and E. coli biofilms.…”

“…60,61,63 Interestingly, similar to EC, low-frequency US (70 kHz) with low acoustic intensity increased the transport of oxygen and nutrients to the cells, thereby killing S. epidermidis, P. aeruginosa, and E. coli biofilms. 62 To further enhance efficacy, insonation of E. coli or P. aeruginosa biofilms with microbubbles has been investigated to improve antibiotic efficacy. 63 For example, US (0.08 MHz) targeted microbubble destruction of biofilm in an in vivo rabbit model enhanced the effects of vancomycin.…”

Treatment of biofilm infections on implants with low-frequency ultrasound and antibiotics

“…For example with biofilms of gram-positive Staphylococcus epidermidis, the application of ultrasound during vancomycin therapy further decreased the viability of the biofilm in vivo (15).…”