Polymethylmethacrylate Antibiotic Bead Chains:

Rationale: -- to deliver levels of antibiotics locally in concentrations that exceed the minimal inhibitory concentrations. -- the local concentrations of antibiotic achieved are 200 times higher than levels achieved with systemic antibiotic administration. -- The antibiotic is leached from the PMMA beads into the postoperative wound hematoma and secretion, which act as a transport medium. -- High concentrations of the antibiotic can be achieved only with primary wound closure. -- If such closure cannot be performed, the wound can be covered with a water-impermeable dressing (bead pouch technique).

Technique: Before the beads are implanted, all infected and necrotic tissue should be adequately dbrided surgically, and all foreign material should be removed. Suction drains are not recommended because the concentration level of the antibiotic is diminished when they are used. The antibiotic bead pouch technique: -- Henry, Ostermann, and Seligson Thoroughly dbride all necrotic tissue as previously described. Irrigate the wound using a pulsatile lavage system with 9 L of saline solution containing bacitracin. Prepare antibiotic PMMA beads by mixing high-viscosity bone cement powder with a powder form of the antibiotic in a bowl. Add the activating solution, and stir the mixture until the cement is workable. Form several beads by rolling them into small spheres. Place the beads on an 18-gauge or 20gauge wire to form a bead chain. Allow the cement to harden. Record the number of beads on the chain to ensure all beads are accounted for on removal. Place the PMMA antibiotic bead chains into the bony defect filling the dead space. Close all wound extensions with interrupted nylon sutures. Dry the skin edges surrounding the wound, and apply a benzoin solution to the skin edges circumferentially.

Apply an adhesive porous polyethylene wound film (OpSite) to cover the wound. A second layer with a larger OpSite or Ioban is placed over the first dressing to prevent leakage.

Aftertreatment:

The limb should be appropriately immobilized. The bead pouch should be changed at 72-hour intervals with repeat dbridement and irrigation until the wound is ready for a soft-tissue coverage procedure.
History: -- The practice of incorporating antibiotic powders into bone cement was initiated in the 1970s as a prophylactic technique.

Materials for bead construction:

1. Polymerized polymethacrylate (PMMA): Bone cement, the traditional material used to prepare antibiotic beads, is composed of a polymerized polymethacrylate (PMMA). This powder is mixed with liquid methylmethacrylate at the time of use. Within minutes, the mixture forms the cement that is used as an adhesive material. If antibiotic beads are needed, antibiotic powder is added to the PMMA powder prior to mixing with the liquid methylmethacrylate. Small beads in varying diameters are then hand-formed from the adhesive material as it begins to set. 2. Calcium sulphate: is sold under the trade name Osteoset in either pellet form or as a kit that includes mold forms to construct beads. The primary clinical application of these products is to serve as dead space fillers during a period of bone regeneration. The beads or pellets slowly resorb over six to 12 weeks at a rate that mimics bone growth. The primary advantage to using such a compound for antibiotic bead delivery is that no second procedure is required for product removal after implantation. Pharmacokinetics: Localized concentrations exceed the MIC for most common pathogens within hours of application. Serum concentrations can be detected but are low (< 1 mcg/mL), and the drug is eliminated from systemic circulation within three to four days of administration. Egs. Palacos G with gentamicin, Simplex P with tobramycin, and Depuy 1 Gentamicin. -- PMMA beads are not biodegradable and therefore, need to be removed after treatment is finished.

Antibiotics used: -- Aminoglycosides are the most commonly employed antibiotics. -- Penicillins, cephalosporins, and clindamycin are eluted well from PMMA beads; -- Vancomycin elutes much less effectively. -- Antibiotics such as the fluoroquinolones, tetracycline, and polymyxin B are broken down during the exothermic process of cement hardening and cannot be used with PMMA beads.

Timing of beads: 1. In short-term implantation, the beads are removed within 10 days, 2. In long-term implantation, they may be left for 80 days

Methods for Bead Removal: 1. The first is to perform a second surgery to extract the majority of beads that were placed. In some instances, methylene blue is added to the cement mixture before hardening to facilitate bead recovery at the time of the second operation. 2. An alternate approach is to form the beads along a surgical wire. This results in a string of beads similar in appearance to a pearl necklace. The end of the wire remains exposed at the completion of the surgical procedure, and the strand is slowly extracted from the wound over a period of weeks to months.

Important considerations
1. Availability of pharmaceutical grade antibiotic powders 2. Antibiotic stability 3. Surface area 4. concerns of potential infection risk

Biodegradable Antibiotic Delivery Systems: -- employ calcium sulfate or calcium phosphate

Animal Studies on Biodegradable Antibiotic Carriers for Osteomyelitis Carrier OI OC Antibiotic Animal Author (y) BMP+ cancellous bone DBM+CaSO4 CaPO4 Hydroxyapatite Biodegradable polymer Biodegradable microspheres Fibrin sealant Collagen sponge X X X X X X Gentamicin Rabbits Li and Hu (2000) Teicoplanin Goats Beardmore et al. (2005) Tobramycin Rabbits Lazarettos et al. (2004) Vancomycin Rabbits Shirtliff et al. (2002) Tobramycin Rabbits Rutledge et al. (2003) Tobramycin Rabbits Ambrose et al. (2004) Tobramycin Rabbits Mader et al. (2002) Gentamicin Rats Mendel et al. (2005)

BMP, bone morphogenetic protein; DBM, demineralized bone matrix; OC, osteoconductive; OI, osteoinductive.

-- By Dr. C. Sakthi Annamalai Ortho PG