Treatment of experimental osteomyelitis by surgical debridement and the implantation of bioerodable, polyanhydride‐gentamicin beads

Abstract

Osteomyelitis was induced in the radius in 77 rabbits and confirmed by histological examination and culture. At 4 weeks, the wounds were debrided and the animals were treated with (a) fatty acid dimer-sebacic acid beads (a bioerodable composite) impregnated with 20% or (b) 10% gentamicin sulfate, (c) placebo beads and intramuscular gentamicin sulfate, (d) placebo beads alone, or (e) debridement only. After 4 weeks, eradication of infection was determined by histological examination and culture. Osteomyelitis was eradicated in 93% of the animals treated with the beads and 20% gentamicin, in 67% of those treated with the beads and 10% gentamicin, in 25% of those treated with placebo beads and intramuscular gentamicin, in 7% of those treated with placebo beads alone, and in 12.5% of those treated with debridement only (p values from < 0.001 to 0.02). Fatty acid dimer-sebacic acid beads with gentamicin were then implanted in noninfected rabbits, and gentamicin sulfate concentrations in bone, serum, urine, and wound exudate were measured. Gentamicin sulfate was detectable in bone for as long as 8 weeks after implantation. Levels as high as 4,746 micrograms/ml were present in the wound exudate for the first 7 days. Levels in the serum peaked at 1.03 micrograms/ml. Urine levels peaked at 135 micrograms/ml.

Jeannette Wilkins Award: Can Locally Delivered Gadolinium Be Visualized on MRI? A Pilot Study

“…Locally delivered Gd-DTPA was visualized from all three vehicles but absent from all control depots at all time points, as expected based on in vitro elution data [23]. Our data for distribution of locally delivered Gd-DTPA in soft tissue are consistent with in vivo tissue delivery measured by Adams et al [1], Nelson et al [22], and Owen et al [24]; with MRI data for drug distribution from a local infusion in vitro by Raghavan et al [26]; and with the local distribution after infusion into brain tissue in vivo [4] (Table 2). Our data showing visualization of Gd-DTPA over time with an MRI are consistent with Astary et al [4] and Raghavan et al [26], who also showed that gadolinium distribution can be seen to change with time.…”

“…Although there are considerable data characterizing in vitro release [1, 2, 7, 9, 11, 14-16, 23, 29], there are few in vivo data reporting antimicrobial distribution after local delivery. Antimicrobial concentration has been measured in bone and soft tissue adjacent to a local delivery in animals [1,22,24]. Adams et al [1] measured antimicrobial concentration in fluid, soft tissue, and bone adjacent to antimicrobial PMMA beads in mongrel dogs.…”

“…Adams et al [1] measured antimicrobial concentration in fluid, soft tissue, and bone adjacent to antimicrobial PMMA beads in mongrel dogs. Nelson et al [22] measured antimicrobial levels in soft tissue and in bone adjacent to local antimicrobial-loaded biodegradable polymer over 6 weeks. Further study by Nelson et al [22] documented the distribution of antimicrobial in avascular bone of rabbit femurs.…”

“…Nelson et al [22] measured antimicrobial levels in soft tissue and in bone adjacent to local antimicrobial-loaded biodegradable polymer over 6 weeks. Further study by Nelson et al [22] documented the distribution of antimicrobial in avascular bone of rabbit femurs. However, these assay techniques require tissue specimens limiting clinical application.…”

Biofilm Antimicrobial Susceptibility Increases With Antimicrobial Exposure Time

“…Local delivery is expected to achieve levels above MBEC for several days. In vivo pilot data from quantitative MRI and in vivo tissue levels are consistent with levels from local delivery of 100 to 2000 lg/ mL lasting 5 days or more indicating the concentrations consistent with expected MBECs can be achieved from local delivery [12,15]. Although MBEC is the concentration that potentially will eradicate biofilm in 24 hours, it is not known if treatment duration longer than 24 hours would require the same antimicrobial concentration.…”