Polylactide/polyglycolide antibiotic implants in the treatment of osteomyelitis. A canine model

Kevin Lloyd Garvin, J. A. Miyano, D. Robinson, D. Giger, J. Novak, Stanley J Radio

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

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 divided into three treatment groups. Group 1 (eight animals [sixteen tibiae]) was treated with parenteral administration of gentamicin (three milligrams per kilogram of body weight per day) every eight hours for four weeks. Group 2 (nine animals [nine tibiae]) was treated with a polymethylmethacrylate implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. Group 3 (nine animals [nine tibiae]) was treated with a polylactide/polyglycolide implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. All animals were killed at the end of treatment. At that time, specimens of tissue were obtained for quantitative culture as well as for antibiotic immunoassay. In the groups that had been treated with an implant, serum was obtained for the measurement of serum drug levels after debridement; after the implantation; four, seven, and twenty-one days postoperatively; and immediately before the animals were killed. The 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 animals were killed averaged 1.6 micrograms per gram in Group 1, 10.3 micrograms 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 per gram in Group 1, 3.2 micrograms per gram in Group 2, and 5.7 micrograms per gram in Group 3. With the numbers studied, there was no significant difference in eradication of the infection between the animals that had been treated with a polymethylmethacrylate-gentamicin implant and those that had been treated with a polylactide/polyglycolide-gentamicin implant. However, there was a significant difference between the animals that had been treated with a polymethylmethacrylate-gentamicin implant and those that had been treated with parenteral administration of gentamicin (p = 0.049) as well as between those that had been treated with a polylactide/polyglycolide-gentamicin implant and those that had been treated with parenteral administration of gentamicin (p = 0.008). Clinical Relevance: Antibiotics are useful in both the prevention and the treatment of deep skeletal infections. Implantable systems for the delivery of antibiotics produce locally sustained, therapeutic drug levels that are effective in the treatment of osteomyelitis. In contrast to parenteral therapy, the systemic levels of antibiotic delivered by local implantation are low or undetectable, minimizing the potential for systemic toxicity. The carrier substance polylactide/polyglycolide is biodegradable, undergoing hydrolysis into naturally occurring lactic and glycolic acids. Although most of the experience with use of lactic and glycolic acid homopolymers and copolymers has been with biodegradable sutures, new applications have been developed, including use in drug delivery systems. This study describes the use of polylactide/polyglycolide 50:50 copolymer as a carrier for the local, controlled delivery of antibiotics for the treatment of osteomyelitis. Additional studies will be necessary to confirm the biocompatibility of polylactide/polyglycolide in humans.

Original languageEnglish (US)
Pages (from-to)1500-1506
Number of pages7
JournalJournal of Bone and Joint Surgery - Series A
Volume76
Issue number10
DOIs
StatePublished - Jan 1 1994

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Polyglycolic Acid
Osteomyelitis
Gentamicins
Canidae
Tibia
Anti-Bacterial Agents
glycolic acid
Polymethyl Methacrylate
Debridement
Infection
Lactic Acid
poly(lactide)
Therapeutics
Drug Delivery Systems
Serum
Immunoassay
Pharmaceutical Preparations
Sutures
Staphylococcus aureus
Hydrolysis

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

Polylactide/polyglycolide antibiotic implants in the treatment of osteomyelitis. A canine model. / Garvin, Kevin Lloyd; Miyano, J. A.; Robinson, D.; Giger, D.; Novak, J.; Radio, Stanley J.

In: Journal of Bone and Joint Surgery - Series A, Vol. 76, No. 10, 01.01.1994, p. 1500-1506.

Research output: Contribution to journalArticle

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abstract = "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 divided into three treatment groups. Group 1 (eight animals [sixteen tibiae]) was treated with parenteral administration of gentamicin (three milligrams per kilogram of body weight per day) every eight hours for four weeks. Group 2 (nine animals [nine tibiae]) was treated with a polymethylmethacrylate implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. Group 3 (nine animals [nine tibiae]) was treated with a polylactide/polyglycolide implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. All animals were killed at the end of treatment. At that time, specimens of tissue were obtained for quantitative culture as well as for antibiotic immunoassay. In the groups that had been treated with an implant, serum was obtained for the measurement of serum drug levels after debridement; after the implantation; four, seven, and twenty-one days postoperatively; and immediately before the animals were killed. The 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 animals were killed averaged 1.6 micrograms per gram in Group 1, 10.3 micrograms 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 per gram in Group 1, 3.2 micrograms per gram in Group 2, and 5.7 micrograms per gram in Group 3. With the numbers studied, there was no significant difference in eradication of the infection between the animals that had been treated with a polymethylmethacrylate-gentamicin implant and those that had been treated with a polylactide/polyglycolide-gentamicin implant. However, there was a significant difference between the animals that had been treated with a polymethylmethacrylate-gentamicin implant and those that had been treated with parenteral administration of gentamicin (p = 0.049) as well as between those that had been treated with a polylactide/polyglycolide-gentamicin implant and those that had been treated with parenteral administration of gentamicin (p = 0.008). Clinical Relevance: Antibiotics are useful in both the prevention and the treatment of deep skeletal infections. Implantable systems for the delivery of antibiotics produce locally sustained, therapeutic drug levels that are effective in the treatment of osteomyelitis. In contrast to parenteral therapy, the systemic levels of antibiotic delivered by local implantation are low or undetectable, minimizing the potential for systemic toxicity. The carrier substance polylactide/polyglycolide is biodegradable, undergoing hydrolysis into naturally occurring lactic and glycolic acids. Although most of the experience with use of lactic and glycolic acid homopolymers and copolymers has been with biodegradable sutures, new applications have been developed, including use in drug delivery systems. This study describes the use of polylactide/polyglycolide 50:50 copolymer as a carrier for the local, controlled delivery of antibiotics for the treatment of osteomyelitis. Additional studies will be necessary to confirm the biocompatibility of polylactide/polyglycolide in humans.",
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T1 - Polylactide/polyglycolide antibiotic implants in the treatment of osteomyelitis. A canine model

AU - Garvin, Kevin Lloyd

AU - Miyano, J. A.

AU - Robinson, D.

AU - Giger, D.

AU - Novak, J.

AU - Radio, Stanley J

PY - 1994/1/1

Y1 - 1994/1/1

N2 - 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 divided into three treatment groups. Group 1 (eight animals [sixteen tibiae]) was treated with parenteral administration of gentamicin (three milligrams per kilogram of body weight per day) every eight hours for four weeks. Group 2 (nine animals [nine tibiae]) was treated with a polymethylmethacrylate implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. Group 3 (nine animals [nine tibiae]) was treated with a polylactide/polyglycolide implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. All animals were killed at the end of treatment. At that time, specimens of tissue were obtained for quantitative culture as well as for antibiotic immunoassay. In the groups that had been treated with an implant, serum was obtained for the measurement of serum drug levels after debridement; after the implantation; four, seven, and twenty-one days postoperatively; and immediately before the animals were killed. The 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 animals were killed averaged 1.6 micrograms per gram in Group 1, 10.3 micrograms 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 per gram in Group 1, 3.2 micrograms per gram in Group 2, and 5.7 micrograms per gram in Group 3. With the numbers studied, there was no significant difference in eradication of the infection between the animals that had been treated with a polymethylmethacrylate-gentamicin implant and those that had been treated with a polylactide/polyglycolide-gentamicin implant. However, there was a significant difference between the animals that had been treated with a polymethylmethacrylate-gentamicin implant and those that had been treated with parenteral administration of gentamicin (p = 0.049) as well as between those that had been treated with a polylactide/polyglycolide-gentamicin implant and those that had been treated with parenteral administration of gentamicin (p = 0.008). Clinical Relevance: Antibiotics are useful in both the prevention and the treatment of deep skeletal infections. Implantable systems for the delivery of antibiotics produce locally sustained, therapeutic drug levels that are effective in the treatment of osteomyelitis. In contrast to parenteral therapy, the systemic levels of antibiotic delivered by local implantation are low or undetectable, minimizing the potential for systemic toxicity. The carrier substance polylactide/polyglycolide is biodegradable, undergoing hydrolysis into naturally occurring lactic and glycolic acids. Although most of the experience with use of lactic and glycolic acid homopolymers and copolymers has been with biodegradable sutures, new applications have been developed, including use in drug delivery systems. This study describes the use of polylactide/polyglycolide 50:50 copolymer as a carrier for the local, controlled delivery of antibiotics for the treatment of osteomyelitis. Additional studies will be necessary to confirm the biocompatibility of polylactide/polyglycolide in humans.

AB - 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 divided into three treatment groups. Group 1 (eight animals [sixteen tibiae]) was treated with parenteral administration of gentamicin (three milligrams per kilogram of body weight per day) every eight hours for four weeks. Group 2 (nine animals [nine tibiae]) was treated with a polymethylmethacrylate implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. Group 3 (nine animals [nine tibiae]) was treated with a polylactide/polyglycolide implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. All animals were killed at the end of treatment. At that time, specimens of tissue were obtained for quantitative culture as well as for antibiotic immunoassay. In the groups that had been treated with an implant, serum was obtained for the measurement of serum drug levels after debridement; after the implantation; four, seven, and twenty-one days postoperatively; and immediately before the animals were killed. The 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 animals were killed averaged 1.6 micrograms per gram in Group 1, 10.3 micrograms 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 per gram in Group 1, 3.2 micrograms per gram in Group 2, and 5.7 micrograms per gram in Group 3. With the numbers studied, there was no significant difference in eradication of the infection between the animals that had been treated with a polymethylmethacrylate-gentamicin implant and those that had been treated with a polylactide/polyglycolide-gentamicin implant. However, there was a significant difference between the animals that had been treated with a polymethylmethacrylate-gentamicin implant and those that had been treated with parenteral administration of gentamicin (p = 0.049) as well as between those that had been treated with a polylactide/polyglycolide-gentamicin implant and those that had been treated with parenteral administration of gentamicin (p = 0.008). Clinical Relevance: Antibiotics are useful in both the prevention and the treatment of deep skeletal infections. Implantable systems for the delivery of antibiotics produce locally sustained, therapeutic drug levels that are effective in the treatment of osteomyelitis. In contrast to parenteral therapy, the systemic levels of antibiotic delivered by local implantation are low or undetectable, minimizing the potential for systemic toxicity. The carrier substance polylactide/polyglycolide is biodegradable, undergoing hydrolysis into naturally occurring lactic and glycolic acids. Although most of the experience with use of lactic and glycolic acid homopolymers and copolymers has been with biodegradable sutures, new applications have been developed, including use in drug delivery systems. This study describes the use of polylactide/polyglycolide 50:50 copolymer as a carrier for the local, controlled delivery of antibiotics for the treatment of osteomyelitis. Additional studies will be necessary to confirm the biocompatibility of polylactide/polyglycolide in humans.

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