Surgical Techniques

Antibiotic Beads
Thomas A. DeCoster, MD Shahram Bozorgnia, MD

The video that accompanies this article is Preparation and Use of Antibiotic-Impregnated Beads for Orthopaedic Infections, available on the Orthopaedic Knowledge Online Website, at http://www5. aaos.org/oko/jaaos/surgical.cfm

Dr. DeCoster is Professor and Vice Chair, Department of Orthopaedics and Rehabilitation, University of New Mexico School of Medicine, Albuquerque, NM. Dr. Bozorgnia is Trauma Fellow, Department of Orthopaedics and Rehabilitation, University of New Mexico School of Medicine. Dr. DeCoster or a member of his immediate family has received research or institutional support from Biomet, EBI, Orthofix, Smith & Nephew, Stryker, and Zimmer; has stock or stock options held in Merck and Wyeth; and has received royalties from Innomed. Neither Dr. Bozorgnia nor a member of his immediate family has received anything of value from or owns stock in a commercial company or institution related directly or indirectly to the subject of this article. Reprint requests: Dr. DeCoster, Department of Orthopaedics and Rehabilitation, University of New Mexico School of Medicine, 1127 University Boulevard NE, Albuquerque, NM 87131. J Am Acad Orthop Surg 2008;16:674678 Copyright 2008 by the American Academy of Orthopaedic Surgeons.

one infection, or osteomyelitis, can be one of the most difficult problems confronted by the orthopaedic surgeon. Common causes of osteomyelitis include open fractures, hematogenous spread of bacteria to bone, and orthopaedic surgical procedures complicated by infection. Assessment involves identification of the offending organism by tissue culture and sensitivity to antibiotics; radiographic assessment of the extent of the infection; clinical evaluation of the patients general health and ability to fight infection; and determination of the local anatomic condition of the bone and soft tissue. Treatment is individualized but generally involves prolonged use of systemic antibiotics, surgical dbridement, and support of the patients overall health.1,2 Results are generally good but are not universally successful. Difficulties include recurrence or lack of control of infection, systemic toxicity to antibiotics, scar formation, and persistent nonunion of fractures.2 Other problems include expense and practical difficulties for the patient and the surgeon, including multiple surgical treatments, lengthy and frequent hospitalizations, and prolonged limb dysfunction. Control of infection eventually may be obtained, but patient function still may be limited by scar, stiffness, and weakness, as well as nonunion or malunion of the fracture. Late recurrence of infection is also a problem. To deliver therapeutic tissue levels of parenteral antibiotics to the target area, high serum levels of antibiotics must be achieved.3 These high serum levels, however, may result in an increased incidence of systemic side effects such as nephrotoxicity and ototoxicity.4 As an alter-

native, the use of antibioticimpregnated beads as an adjunct to other treatment offers advantages compared with systemic aminoglycosides. With the bead pouch technique, the systemic levels are low, and the systemic complications are virtually eliminated, while the local concentration, where it is needed, is extremely high.3 Antibiotic beads also offer the benefit of management of dead space. They are relatively inexpensive and are easy for the surgeon to insert and the patient to tolerate.5

Indications and Contraindications

Antibiotic beads can be used in multiple different applications. Typical indications include prevention of infection (eg, open fracture antibiotic bead pouch prophylaxis), treatment of established bone infection (ie, acute and chronic osteomyelitis), treatment of infected joint arthroplasties, dead space management in patients with large soft-tissue injuries, and chronic infected nonunions. Contraindications to the use of antibiotic bead pouches in the treatment of open fractures include patient hypersensitivity to specific antibiotics, small wounds (for which beads are not necessary), and unsalvageable limbs (because beads do not overcome massive tissue injuries). Contraindication to the use of antibiotic beads in the treatment of osteomyelitis include patient hypersensitivity to a specific antibiotic and the presence of resistant and slime-forming organisms such as Enterococcus. The foreign-body surface of the methacrylate beads themselves is conductive to slimeproducing organisms, and the slime

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Journal of the American Academy of Orthopaedic Surgeons

Thomas A. DeCoster, MD, and Shahram Bozorgnia, MD

barrier severely limits the efficacy of the antibiotics in controlling the infection.6,7

Figure 1

Figure 2

Specific Characteristics of Antibiotic Beads

Antibiotic-impregnated polymethylmethacrylate (PMMA) cement beads are a popular modality used in conjunction with surgical dbridement and intravenous antibiotic therapy for the treatment or prophylaxis of orthopaedic infections. The beads vary in size, type and amount of antibiotic used, and type of bone cement used. The beads can be prepared in advance by molding or by rolling by hand in the operating room. Nonbiodegradable PMMA cement is the most common carrier used. To incorporate antibiotics, antibiotic powder is mixed with the powdered cement polymer before adding the methylmethacrylate liquid monomer. The antibiotic must be water soluble, available as powder, able to remain stable despite the heat generated during the polymerization reaction, and hypoallergenic, as well as have a broad spectrum of activity. Antibiotic release is highest in the first 4 days following implantation; the remaining elution at therapeutic concentration persists for weeks to months.8 Wahlig et al3 showed that, if gentamicin-PMMA chains are implanted and the wound is closed, then the local concentrations of antibiotic achieved are 200 times the levels achieved with systemic antibiotic administration. However, the use of the beads in an open system or in combination with suction irrigation rapidly lowers local antibiotic concentrations, and the therapeutic advantage is diminished. Therefore, this technique is not recommended. Aminoglycosides are the most commonly used antibiotics in this context. They are effective against aerobic gram-negative bacilli and staphylococci as well as streptococVolume 16, Number 11, November 2008

A string of antibiotic beads is placed into the wound for dead space management and to provide a high concentration of local antibiotic to the wound.

In open fractures with significant softtissue injuries, antibiotic beads can be placed in the open wound. The softtissue defect will be covered with an adhesive, porous, polyethylene wound film.

ci, enterococci, and anaerobes.9 Among the aminoglycosides are tobramycin and gentamicin. Tobramycin has been substituted for gentamicin in the United States because it is available as a pharmaceuticalgrade powder, whereas gentamicin is not. There is extensive information on the elution patterns of aminoglycosides from beads in a variety of clinical scenarios.4,10 Vancomycin should be considered when there is a risk of resistant staphylococcal organisms, that is, methicillin-resistant Staphylococcus aureus. Vancomycin is available in powder form and is not neutralized by the heat of methacrylate polymerization. Effective elution of vancomycin has also been reported.11 Bead molds are available in a variety of sizes. A diameter of 8 mm is the largest and 2 mm, the smallest. Small-diameter beads are used in wounds of the hand and in other small wounds to maximize the surface area and antibiotic elution. Consistency in size and shape of the beads also facilitates their passage into tight spaces, including the medullary canal.

Surgical Technique
The technique of application of antibiotic beads involves the production

of beads, followed by surgical placement within the dbrided wound and in place of dbrided bone (Figures 1 and 2). Following bead implantation, the soft tissue is closed. The beads allow for very high levels of antibiotic bathing of the wound and also assist in fighting infection. The beads occupy space, preventing the accumulation of hematoma that otherwise would be a potential site for infection. Antibiotic beads also provide management of dead space by preventing the formation of scar tissue in the bone-defect site. If infection persists, a repeat dbridement, culture, and antibiotic bead exchange may be performed after several days or weeks. Once the infection is well controlled, the beads are surgically removed. For nonunion or a large bone void, bone graft may be placed in the area that the beads occupied. Although the antibiotic within the beads produces a high local concentration in the surrounding tissues, the systemic level of antibiotic resulting from beads is low, which minimizes complications, including renal toxicity and ototoxicity. The high local concentration of antibiotic reduces and often eliminates the need for intravenous antibiotics; therefore, intravenous access and compliance are not required. Osteomyelitis typically involves seques675

Antibiotic Beads

Figure 3

Figure 4

The liquid cement mixture is pressed forcefully with a tongue depressor into the bead mold.

The liquid cement mixture is pressed forcefully with a cement-filled syringe into the bead mold.

tration of dead infected bone with little to no blood supply. Many systemic antibiotics exhibit poor penetration of bone, even when the bone is vascularized. Hence, systemic antibiotics and blood-borne antimicrobial cells may not reach the area of greatest need. Antibiotic beads, however, provide high local concentrations of antibiotic not dependent on blood supply to the bone. Neither are the antibiotics dependent on bone penetration.5

Antibiotic Bead Preparation Technique

Bead Preparation The bead preparation technique described here results in spherical, uniform tobramycin-impregnated video, IngrediPMMA beads ( ents). These beads can be made in advance, sterilely packaged, and stored in the operating room ready for use. Alternatively, beads can be prepared in the operating room at the time of implantation, with or without the use of bead molds. When this technique is used, sufficient time (at least 30 minutes) must be allowed for full curing of the cement to minimize toxic monomers. Materials The materials needed for the production of tobramycin-impregnated PMMA beads are the following: One package (40 g) of PMMA
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bone cement 20 mL of liquid monomer Two 1.2-g vials of tobramycin powder Two twisted strands of 26-gauge wire A cast-metal, Teflon-coated bead mold One medium-size (approximately 200 mL) plastic bowl Tongue depressors Two 10-mL syringes Tweezers from a suture-removal kit Gloves Technique Twist together two strands of 26gauge wire (50 turns using a hand video, Wire-Twisting Prodrill) ( cedure). Carefully place the wire into the grooves of the bead mold video, and tighten the mold ( Preparation Technique A [Spatula]). A cool working environment and precooling of the mold and PMMA prolong the polymerization time. In a medium-size plastic bowl, mix most of one package of bone cement (ie, 35 of 40 g) with two 1.2-g vials of tobramycin powder. This allows a prolonged liquid phase, which facilitates better bead production. Stir thoroughly to ensure homogeneity of the mixture. Pour 20 mL of liquid monomer into the powder and stir vigorously for about 30 seconds until the mixture liquefies. Continue to stir the cement mixture, mov-

ing the cement away from the bottom and edges of the bowl to prevent hardening. With a tongue depressor, forcefully press the liquid cement mixture into the bead mold (Figure 3). Quickly and carefully fill all of the holes until the entire mold is filled with the cement mixture. It is imperative that this step is done in less than 8 minutes, before the mixture hardens. Smooth the surface of the mold by scraping off the remaining cement with a tongue depressor. Place the mold on its side and let it sit for 15 minutes as the cement hardens. An alternative technique for placing the cement into the mold holes is to pour 3 mL of the liquid cement mixture into a 10-mL syringe with the plunger removed and the tip capped, then replace the plunger and video, remove the syringe cap ( Preparation Technique B [Syringe]). While applying pressure, use the syringe to fill each hole in the mold with the cement mixture. Keep the syringe at a 90 angle as each hole is filled and apply pressure to maintain a tight seal between the mold and the syringe (Figure 4). Cement should bulge into the adjacent hole. Proceed rapidly because the syringe technique requires the cement to be in the liquid state. Four syringes typically are needed for two 20-bead chains. The tip of each syringe is cut off so that the lumen matches the diameter of the mold. Smooth the surface of the mold by scraping off the remaining cement with a tongue depressor. Place the mold on its side and let it sit for 15 minutes until the cement is completely hardened. After 15 minutes, take the mold apart and gently remove the beads by pulling the wire (Figure 5). Remove the excess cement (ie, flashing) between the beads using the tweezers from the suture kit. Excess cement in the mold also should be removed to facilitate the next use of the mold. A pair of scissors from a suture-removal set is the exact

Journal of the American Academy of Orthopaedic Surgeons

Thomas A. DeCoster, MD, and Shahram Bozorgnia, MD

Pearls Remove all avascular, necrotic, and contaminated tissue before applying antibiotic beads. Infection resulting from inadequate dbridement will not be overcome by the use of antibiotic beads. Beads can be made in advance and stored in the operating room. Thoroughly mix the bone cement with the antibiotic powder before adding the liquid monomer. Fill all of the holes of the mold as quickly as possible before the mixture hardens. An assistant is helpful. Pitfalls Do not use the beads in an open system or in combination with suction irrigation because doing so prevents development of effective antibiotic levels in the wound. Do not use the beads as an initial measure in inflamed and suppurating wounds. Do not use the beads in the treatment of osteomyelitis in the presence of resistant organisms or slimeforming organisms (eg, Enterococcus) because effective elution of antibiotic is not achieved. Do not substitute antibiotic beads for thorough wound dbridement. Do not insert handmade beads that are too large to fit into the medullary canal or too big to completely fill the wound. Use care to produce bead chains in a timely fashion during the short available working time (8 minutes) as the methacrylate polymerizes. Failure to do so results in wasted material and surgeon frustration. These can be avoided by planning and relying on an assistant. Do not leave beads in the patient so long (>3 weeks) that removal is difficult.

width of the slots in the mold and thus can be used to remove residual cement from the mold. Transfer the beads into gassterilization packages (Figure 6) and have them sterilized. Wash your hands and all work surfaces thoroughly after working with the cement. This same process can be performed in the operating room, using sterile technique, for immediate use.

Complications
Complications caused by the use of antibiotic beads are uncommon; however, difficulty with bead removal can occur when the beads are left in place too long, especially in the medullary canal of long bones. Antibiotic beads reduce the rate of infection in open fractures, but they do not eliminate the risk. Beads help to control established infections, but not all infections will completely resolve. A major complication is persistent or recurrent infection. Also, spacers can fragment or dislodge when
Volume 16, Number 11, November 2008

subjected to excessive or chronic loads. Infection resulting from inadequate dbridement will not be overcome by the use of antibiotic beads. Knowledge of the effectiveness of antibiotic beads is limited. The optimal dose, duration of treatment, and relative efficacy of various antibiotic classes are not known. Differential elution of antibiotics from various forms of PMMA has been reported,12,13 but the ideal carrier medium is still a matter of debate. The role and efficacy of absorbable beads is not yet known. Local antibiotic delivery by pump or other mechanism is an alternative route of local antibiotic therapy. In addition, the efficacy of beads compared with the efficacy of other delivery methods is not yet known.

Figure 5

After 15 minutes, the mold is taken apart, and the beads are gently removed by pulling the wire. Figure 6

Summary
Antibiotic beads are an attractive method of treatment in the management and prevention of osteomyelitis. Antibiotic beads provide high local concentrations of antibiotic at

The beads are transferred into gassterilization packages. 677

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the site of infection without significant systemic toxicity. A variety of techniques to provide local antibiotics has been reported, including absorbable beads with various types of antibiotics, antibiotic sticks, coated nails, and coated joint spacers. Beads can be prepared in the operating room or in advance. Antibiotic beads assist in dead space management and help facilitate the filling of bone voids and healing of infected nonunions. Results demonstrate improved efficacy in the control of infection and enhanced outcomes, with financial and practical savings.14

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References
Citation numbers printed in bold type indicate references published within the past 5 years.
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