POLYLACTIDE POLYGLYCOLIDE ANTIBIOTIC IMPLANTS IN THE TREATMENT OF OSTEOMYELITIS - A CANINE MODEL/

Osteomyelitis with Staphylococcus aureus was established in the tibiae of twenty-six adult mongrel dogs. After confirmation of infection at four weeks, all animals had operative debridement and were then divide d into three treatment groups. Group 1 (eight animals [sixteen tibiae] ) was treated with parenteral administration of gentamicin (three mill igrams per kilogram of body weight per day) every eight hours for four weeks. Group 2 (nine animals [nine tibiae]) was treated with a polyme thylmethacrylate implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. Group 3 (nine animals [nine tib iae]) was treated with a polylactide/polyglycolide implant containing 100 milligrams of gentamicin that was placed in the tibia for six week s. All animals were killed at the end of treatment. At that time, spec imens of tissue were obtained for quantitative culture as well as for antibiotic immunoassay. In the groups that had been treated with an im plant, serum was obtained for the measurement of serum drug levels aft er debridement; after the implantation; four, seven, and twenty-one da ys postoperatively; and immediately before the animals were killed. Th e infection was eradicated in ten of the sixteen tibiae in Group 1, in eight of the nine tibiae in Group 2, and in all nine tibiae in Group 3. The level of gentamicin in the bone samples at the time that the an imals were killed averaged 1.6 micrograms per gram in Group 1, 10.3 mi crograms per gram in Group 2, and 20.1 micrograms per gram in Group 3; the level of gentamicin in the soft tissues averaged 0.3 microgram pe r gram in Group 1, 3.2 micrograms per gram in Group 2, and 5.7 microgr ams per gram in Group 3. With the numbers studied, there was no signif icant difference in eradication of the infection between the animals t hat had been treated with a polymethylmethacrylate-gentamicin implant and those that had been treated with a polylactide/polyglycolide-genta micin implant. However, there has a significant difference between the animals that had been treated with a polymethylmethacrylate-gentamici n implant and those that had been treated with parenteral administrati on of gentamicin (p = 0.049) as well as between those that had been tr eated with a polylactide/polyglycolide-gentamicin implant and those th at had been treated with parenteral administration of gentamicin (p = 0.008). CLINICAL RELEVANCE: Antibiotics are useful in both the prevent ion and the treatment of deep skeletal infections. Implantable systems for the delivery of antibiotics produce locally sustained, therapeuti c drug levels that are effective in the treatment of osteomyelitis. In contrast to parenteral therapy the systemic levels of antibiotic deli vered by local implantation are low or undetectable, minimizing the po tential for systemic toxicity. The carrier substance polylactide/polyg lycolide is biodegradable, undergoing hydrolysis into naturally occurr ing lactic and glycolic acids. Although most of the experience with us e of lactic and glycolic acid homopolymers and copolymers has been wit h biodegradable sutures, new applications have been developed, includi ng use in drug delivery systems. This study describes the use of polyl actide/polyglycolide 50:50 copolymer as a carrier for the local, contr olled delivery of antibiotics for the treatment of osteomyelitis. Addi tional studies will be necessary to confirm the biocompatibility of po lylactide/polyglycolide in humans.