Antibiotic-impregnated cement and beads for orthopedic infections.

There is a long history of local antibiotic use for the treatment of orthopedic infections (13, 19, 25, 34). During World War I, Alexander Fleming observed that locally applied antiseptics failed to sterilize chronically infected wounds, but they did reduce the burden of bacteria. He also appreciated that leukocytes and tissue fluids were important factors in creating a physiological environment for promoting resolution (19). The sulfonamides were the first antimicrobial agents available for clinical use. In 1939, the instillation of sulfanilamide crystals, along with thorough debridement, hemostasis, primary closure, and immobilization, resulted in a reduced infection rate for open fractures (25). As additional systemic antimicrobial agents became available, interest in the topical treatment of wounds waned, but the management of established osteomyelitis remained problematic. In the 1960s, the method of closed wound irrigation-suction was popularized as a method which could be used to deliver high concentrations of an antibiotic after debridement. The high flow rate of hypertonic solutions by this technique eliminated hematoma accumulation and promoted the influx of leukocytes and tissue fluids. Primary closure could be accomplished to reduce cross contamination (13). An alternative method for delivering high concentrations of an antibiotic to sites of lower extremity osteomyelitis was isolation perfusion. After thorough debridement, cannulae were inserted into the appropriate artery and vein, a tourniquet was placed proximally, and oxygenated blood containing high concentrations of antibiotic was pumped through the limb (34). The antibiotics available for the prevention and treatment of bone infections in the early 1960s were limited. Those that were used primarily included penicillin G, chloramphenicol and the tetracyclines; streptomycin and vancomycin were perceived to be toxic. The cumbersome methods of closed wound irrigation-suction and isolation perfusion were largely abandoned with the subsequent development of new systemic antibiotics which were more potent against the staphylococci and gram-negative bacilli causing orthopedic infections. Included were the antistaphylococcal and broad-spectrum penicillins, cephalosporins, lincosamides, and aminoglycosides and, more recently, the carbapenems and fluoroquinolones. Additionally, vancomycin preparations were purified, and vancomycin was no longer perceived to be highly toxic. The local use of antibiotics to prevent and treat skeletal infections was revived in Germany with the widespread use of prosthetic joint replacement, a situation in which infections were not an anticipated consequence of trauma or sepsis but a devastating complication of elective surgery. In 1970, Buchholz and Engelbrecht (8) reported that penicillin, erythromycin, and gentamicin incorporated into the cement used to attach total hip joint prostheses diffused out into the surrounding tissues over a period of months, thereby providing prolonged concentrations of local antibiotic. On the basis of the success noted in reducing early postoperative arthroplasty infections (8), interest developed in applying antibiotic-impregnated cement as a therapy for osteomyelitis. In 1979, as an alternative to introducing large deposits of antibiotic-impregnated cement at sites of chronic osteomyelitis, Klemm (29) formed gentamicin-impregnated cement into beads and used them to temporarily fill in the dead space created after the debridement of infected bone. Among 128 patients so treated for chronic osteomyelitis, he reported a 91.4% cure rate. Currently, antibiotic-impregnated cement is used to prevent infections primarily in arthroplasties, in which materials with adhesive properties are required; systemic perioperative prophylactic antibiotics are often given as well. Beads are used to temporarily (usually weeks to months) provide high local antibiotic concentrations and fill the dead space after debridement in patients with chronic osteomyelitis or compound fractures; again, systemic antibiotics may be given as well. After granulation tissue forms, the beads are removed and a bone graft is place (17). Despite high initial interest in the use of antibiotic-impregnated cement and beads, controversies remain regarding their indications because of limited proof of efficacy and concerns regarding the consistency and safety of the various products available. In a 1992 survey (17), only 90 (27%) of 336 U.S. hospitals responding to the survey indicated that their physicians used antibiotic-impregnated bone cement or beads, and their use in most hospitals was only occasional. Nearly all of the 90 hospitals used the cement, but less than half used the beads.