Session II - Basic Science
Treatment Efficacy of a Polycaprolactone Bioabsorbable Antibiotic Delivery System
Jeffrey O. Anglen, MD; Bridget S. Rutledge; David R. Huyette, MD; Delbert Day, PhD, University of Missouri, Columbia, MO
Purpose: To compare the treatment efficacy of implantable tobramycin delivery using polycaprolactone (PCL) rods to that of polymethylmethacrylate (PMMA) rods in a rabbit model of staphylococcal osteomyelitis and to evaluate the tissue toxicity of the PCL-tobramycin complex.
Methods: Osteomyelitis of the left proximal femur was initiated via inoculation of 106 CFU Staphylococcus aureus. Two weeks later, rabbits were treated according to one of four regimens. Eleven animals were treated with irrigation only. Twelve animals were treated with both irrigation and placement of a PMMA rod containing tobramycin 6% by weight. Twelve animals were treated with irrigation and placement of a PCL rod without antibiotic. Twelve animals were treated with irrigation and placement of a PCL rod containing 6% tobramycin by weight. Animals in each group were sacrificed at 1, 2, 4, and 8 weeks. Specimens from the rods and the surrounding bone were cultured. Histologic analysis of specimens of the proximal femur and other organs and tissues was performed to evaluate any adverse effects of the treatment.
Results: Fifty-two rabbits were initially inoculated, and five died within 3 days of their inoculation. Blood cultures were positive for S. aureus, and autopsy results were consistent with staphylococcal sepsis as the cause of death. The results from bone, rod, and wound tissue cultures revealed a significant difference between the irrigation-group animals and the PCL-tobramycin group animals, Fisher exact test, P = 0.023. There was also a significant difference between the irrigation group animals and PMMA-tobramycin group animals, Fisher exact test, P = 0.042. There was no difference between the PMMA-tobramycin and the PCL-tobramycin, or between the irrigation and the PCL-alone groups. Histologic analysis of multiple tissue specimens, including brain, thymus, heart, lungs, liver, spleen, pancreas, adrenals, kidneys, lymph nodes, bladder, ovaries and uterus or testicles, and left femur revealed no evidence of toxicity.
Discussion: Infection is a potentially disastrous complication of traumatic musculoskeletal injuries. Traditionally, osteomyelitis has been treated with surgical debridement and irrigation, along with the administration of systemic antibiotic therapy. However, systemic antibiotics may not adequately reach tissues with impaired vascularity, a common condition in musculoskeletal infection. In addition, systemic antibiotics often cause a serious toxic effect in non-target tissues and organs. Local antibiotic delivery may be safer and more effective. The most commonly used local antibiotic delivery vehicle is PMMA; however, it does have drawbacks. The PMMA beads must be surgically removed, involving risk and cost to the patient. PMMA is relatively inefficient at antibiotic delivery; the release of antibiotic has been shown to be limited to 100 mm from the surface. The presence of the PMMA itself is inhibitory to the host immune response, and bacteria can colonize the beads in vivo. PCL, recently demonstrated as an antibiotic carrier by Burd et al., is advantageous in that its molecular weight can be manipulated to determine both an elution rate of the antibiotic and a degradation rate of the polymer. Previous studies have shown that in vitro and in vivo, PCL delivers more drug per unit time than PMMA carriers. The results of this study showed that the treatment efficacy in an animal model was similar for both carriers and that no discernible tissue toxicity from the PCL-tobramycin combination was evident when a wide variety of body tissue specimens were examined. This result, coupled with the reduction in need for subsequent removal surgery, suggests that PCL is a superior implantable drug delivery carrier.
Conclusion: Implantable antibiotic delivery with use of a biodegradable polymer (PCL) demonstrates equal efficacy to the use of PMMA as a carrier in an animal model of staphylococcal osteomyelitis, with no discernible toxicity.
· The FDA has not cleared this drug and/or medical device for the use described in this presentation(i.e., the drug or medical device is being discussed for an "off label" use).