treatment of chronic osteomyelitis with a biodegradable antibiotic-impregnated implant, The

Journal of Orthopaedic Surgery, Jun 2002 by Gitelis, Steven, Brebach, Gregory T

ABSTRACT

The use of local antibiotics from a biodegradable implant for chronic osteomyelitis is an attractive alternative. The implant delivers high tissue levels, obliterates dead space, aids bone repair and does not need to be removed. The purpose of this paper is to review our early clinical experience with custom-made calcium sulfate (Osteoset bone void filler) antibiotic-- impregnated implants.

Key words: osteomyelitis, implant, antibiotic, calcium sulfate, biodegradable

INTRODUCTION

The treatment of chronic osteomyelitis includes debridement of the dead infected tissue, obliteration of dead space, osseous repair, adequate soft tissue coverage, and systemic antibiotics. The delivery of antibiotics to bone varies considerably. Oral antibiotics are unpredictable with relatively low bone levels and are infrequently used. Intravenous antibiotics are used commonly in the treatment of chronic osteomyelitis. The appropriate drug is selected based on bacterial sensitivity and an adequate serum level is maintained. Six weeks of intravenous antibiotics is necessary for adequate therapy. Even with prolonged intravenous antibiotics, there is a significant relapse rate. To supplement systemic antibiotics, local antibiotic delivery has been tried for many years. Local antibiotic delivery can be achieved by mechanical pumps, nonbiodegradable implants such as methylmethacrylate, or a biodegradable implant.

Local antibiotic delivery has the advantage of high-- tissue concentrations with relatively low serum levels. This avoids some of the toxicity associated with systemic antibiotics, especially aminoglycosides. Antibiotic-impregnated implants are particularly attractive because not only do they deliver high tissue levels of antibiotics but they also help obliterate the dead space that occurs after bone debridement.1,6,9,18 Antibiotic pumps do not achieve this desirable effect.

The most common form of local antibiotic delivery by an implant is with the use of methylmethacrylate. Various types of methylmethacrylate have been tested by elution studies.2,13,14 The shape of the methylmethacrylate implant along with the type of methylmethacrylate has a significant effect on the amount of antibiotic delivery, as well as duration. Tobramycin, gentamicin, and vancomycin are the antibiotics that have been combined with methylmethacrylate. Nelson et al13 found the delivery of both gentamicin and tobramycin at day one ranged from 88 to 807 (mu)g/ml. There was a significant dropoff in the amounts at day two, and a much more gradual decrease out to 30 days. By day 30, between 1 and 28 (mu)g/ml of antibiotic was delivered. The best delivery profile was with Septopal(R). Septopal(R) beads consist of Palacos(R) cement impregnated with gentamicin.15 Several authors have shown the local delivery of antibiotics is quite effective in eradicating osteomyelitis. Animal models of osteomyelitis have been used to test the effectiveness of local antibiotic delivery.6 The results suggest that the eradication of bacteria can be accomplished more effectively with local antibiotic delivery over systemic therapy. Methylmethacrylate is not an ideal antibiotic implant. It is a dense acrylic, nonbiodegradable, and generally needs to be surgically removed to avoid becoming a future nidus. Finally, methylmethacrylate does not aid in bone repair. As a result, there has been increased interest in the use of a biodegradable antibiotic implant to treat chronic osteomyelitis. One of the most well known materials studied is calcium sulfate.3,4,7,8,11 Calcium sulfate is a bioceramic that occurs naturally. Surgical-grade calcium sulfate is a relatively pure alpha hemihydrate crystal, which can be hydrated producing solid implants. Any water-soluble antibiotics can be incorporated into the crystalline structure, thus loading the implant with antibiotics. Aminoglycosides and vancomycin have been used in this manner. Calcium sulfate is well tolerated, nonimmunogenic, and fully biodegradable.

The rate of resorption is dependent upon the density of the crystal. Implants can resorb either quickly or slowly depending upon how they are produced. Elution testing of 4% by weight loaded calcium sulfate pellets revealed a maximum concentration of 828 (mu)g/ml and undetectable levels by day 15. In vivo measurements of antibiotic delivery from calcium sulfate have also been performed. Calcium sulfate pellets impregnated with 2% and 4% by weight of tobramycin were tested in the dog humerus.17 Systemic levels peaked at one hour (1.8 (mu)g/ml and 3.6 (mu)g/ml for the 2% and 4% concentrations, respectively) and was undetectable by 24 hours.

Tissue levels reached a mean 1,964 (mu)g/ml (2%) and 3,297 (mu)g/ml (4%) at one hour. By day 14, the tissue level was 2 (mu)g/ml (2%) and 4 (mu)g/ml (4%) and was greater than 0.1 (mu)g/ml for up to 28 days. Not only did these calcium sulfate implants fully degrade, they aided in the bone repair. This is an added value when treating osteomyelitis.8,10,12,17,19 Sulo (1993) reported on 409 patients from Albania treated with plaster of Paris antibiotic beads impregnated with gentamicin. 95% of these patients were felt to be cured of chronic osteomyelitis after 37 months mean follow-up. 42% of the patients had complete filling of the osseous defect with this technique. The purpose of this paper is to present our early clinical experience with calcium sulfate as a local antibiotic delivery implant for chronic osteomyelitis. Infection control and bone repair will be reported.