In Vitro Elution Characteristics of PMMA Cement Intramedullary Spacers Impregnated with Vancomycin and Tobramycin
Methods: Two antibiotic-impregnated bone cement groups were prepared. Group 1 (Beads) contained 1.0 g vancomycin and 1.2 g tobramycin mixed in 40 g PMMA and rolled into spheres. Group 2 (Nails) consisted of 2.0 g vancomycin, 2.4 g tobramycin and 80 g PMMA fabricated into an IMN. Ten samples were made for each group. Concentrations of antibiotics eluted from the specimens were then measured and compared.
Results: Group 1 showed high rates of elution early with logarithmic release of vancomycin; however, by the 7th day its concentration dropped below detection (<5 μg/ml). Group 2 showed early elution of vancomycin of less than one third that of Group 1, and by the 3rd day the concentration fell below detection. Although brief, this difference was statistically significant (P<0.004). The elution rates of tobramycin showed high rates of release with exponential decay as seen with vancomycin. At each time point, beads showed higher elution rates than nails up to 4 weeks. The mean totals of tobramycin released were 296.0 μg in Group 1 and 81.9 μg in Group 2.
Discussion: Antibiotics elute at a higher rate from PMMA beads than from PMMA IMNs.
Keywords: Septic nonunion; Local antibiotic release; Antibiotic elution kinetics.
Septic nonunion following intramedullary stabilization of tibial shaft fractures is a serious complication. Overall incidence of deep infection increases from about 1% in closed fractures  to as high as 9% in open tibial shaft fractures . Removal of the intramedullary nail (IMN) is typical, which poses two problems: loss of stability of the fracture and a non-collapsible cavity hindering local delivery of antibiotics .
External fixation with intramedullary antibiotic impregnated polymethylmethacrylate (PMMA) bone cement beads has been used to address these issues; however, this has several disadvantages, including pin tract infections and decreased patient mobility . Various antibiotic cement-coated IMN techniques have since been described to treat the infection and provide bone stability necessary for fracture healing [5-7]. This technique has shown positive results; however, in a study by Thonse & Conway, 21% of patients required additional procedures after placement of antibiotic IMNs for treatment of infection . As antibiotic PMMA beads and small spacers are historically left in place for 6-8 weeks to treat various orthopedic infections [9,10], it has become the consensus among orthopedists that IMNs also remain 6-8 weeks as is reflected in the literature [5-8]. Although elution kinematics have been described for cement spacer blocks and beads [11-15], no study has evaluated the elution properties of long, cylindrical intramedullary cement spacers. Our hypothesis is that these IMNs will have elution kinematics inferior to PMMA beads; supportive results raise questions about the duration of intramedullary treatment. MATERIALS & METHODS
The elution rates of vancomycin from the Group 1 (Beads) and Group 2 (Nails) are shown in Figure 3. Group 1 (Beads) showed high rates of elution early with logarithmic release of vancomycin; however, by the 7th day of testing the concentration dropped below the detection threshold of 5 μg/ml. The early elution of vancomycin in Group 2 (Nails) was less than one third that of Group 1 (Beads) and by the 3rd day of testing the concentration fell below 5 μg/ml. Despite the brevity of the results, this difference was statistically significant (p<0.004).
The elution rates of tobramycin from Group 1 (Beads) and Group 2 (Nails) are shown in Table 1. High rates of antibiotic release occurred early with exponential decay as with vancomycin (Figure 4). At each time point, beads showed higher elution rates than nails with statistical significance shown through week 5 of testing. The mean total of tobramycin released was 296 μg in Group 1 (Beads), and 81.9 μg in Group 2 (Nails.)
 Blachut PA, O’Brien PJ, Meek RN, Broekhuyse HM. Interlocking intramedullary nailing with and without reaming for the treatment of closed fractures of the tibial shaft. A prospective, randomized study. J Bone Joint Surg Am. 1997;79:640-6.
 Papakostidis C, Kanakaris N, Pretel J. Prevalence of complications of open tibial shaft fractures stratified as per the Gustilo–Anderson classification. Injury. 2011;42:1408-15.
 Tetsworth K, Cierny G. Osteomyelitis debridement techniques. Clin Orthop Relat Res 1999;360:87-96.
 Green SA. Complications of external skeletal fixation. Clin Orthop Relat Res. 1983;180:109-16.
 Thonse R, Conway J. Antibiotic cement coated interlocking nail for the treatment of infected nonunions and segmental bone defects. J Orthop Trauma. 2007;21:258-68.
 Paley D, Herzenberg JE. Intramedullary infections treated with antibiotic cement rods: preliminary results in nine cases. J Orthop Trauma. 2002;16:723-9.
 Ohtsuka H, Yokoyama K, Higashi K, Tsutsaumi A, Fukushima N, Noumi T, Itoman M. Use of antibiotic-impregnated bone cement nail to treat septic nonunion after open tibial fracture. J Trauma. 2002;52:364-6.
 Thonse R, Conway JD. Antibiotic cement-coated nails for the treatment of infected nonunions and segmental bone defects. J Bone Joint Surg Am. 2008;90(Suppl 4):163-74.
 Scott IR, Stockley I, Getty CJ. Exchange arthroplasty for infected knee replacements. A new two-stage method. J Bone Joint Surg Br. 1993;75:28-31.
 Wininger DA, Fass RJ. Antibiotic-impregnated cement and beads for orthopedic infections. Antimicrob Agents Chemother. 1996;40:2675-9.
 Adams K, Couch L, Cierny G, Calhoun J, Mader JT. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res. 1992;278:244-52.
 Holtom PD, Warren CA, Greene NW, Bravos PD, Ressler RL, Shepherd L, McPherson EJ, Patzakis MJ. Relation of surface area to in vitro elution characteristics of vancomycin-impregnated polymethylmethacrylate spacers. Am J Orthop (Belle Mead NJ). 1998;27:207-10.
 Penner MJ, Masri BA, Duncan CP. Elution characteristics of vancomycin and tobramycin combined in acrylic bone-cement. J Arthroplasty. 1996;11:939-44.
 Klekamp J, Dawson J, Haas DW, DeBoer D, Christie M. The use of vancomycin and tobramycin in acrylic bone cement: biomechanical effects and elution kinetics for use in joint arthroplasty. J Arthroplasty. 1999;14:339-46.
 Masri BA, Duncan CP, Beauchamp CP, Paris NJ, Arntorp J. Effect of varying surface patterns on antibiotic elution from antibiotic-loaded bone cement. J Arthrosplasty. 1995;10:453-9.
 Marks KE, Nelson CL, Lautenschlager EP. Antibiotic-impregnated acrylic bone cement. J Bone Joint Surg Am.1976;58:358-64.
 Penner MJ, Duncan CP, Masri BA. The in vitro elution characteristics of antibiotic-loaded CMW and Palacos-R bone cements. J Arthroplasty. 1999;14:209-14.
 Bhadra AK, Roberts CS. Indications for antibiotic cement nails. J Orthop Trauma 2009;23(Suppl 5):S26-30.
 Wasko M, Borens O. Antibiotic cement nail for the treatment of posttraumatic intramedullary infections of the tibia: Midterm results in 10 cases. Injury. 2013;44:1057-60.