Antimicrobial Mechanisms and Preparation of Antibiotic-impregnated Cement-coated Locking Plates in the Treatment of Infected Non-unions
Robert Kaspar Wagner, Clara Guarch-Pérez, Alje P van Dam, Sebastian AJ Zaat, Peter Kloen
Antibiotic, Cement, Infection, In vitro, Non-union, Osteosynthesis, Plate
Citation Information :
Wagner RK, Guarch-Pérez C, Dam AP, Zaat SA, Kloen P. Antimicrobial Mechanisms and Preparation of Antibiotic-impregnated Cement-coated Locking Plates in the Treatment of Infected Non-unions. 2023; 18 (2):73-81.
Background: Antibiotic-impregnated cement-coated plates (ACPs) have been used successfully for temporary internal fixation between stages in the two-stage treatment of infected non-unions. We describe our approach of using an ACP in the staged treatment of a methicillin-resistant Staphylococcus aureus (MRSA)-infected distal femoral non-union below a total hip prosthesis. In addition, we present the results of an in vitro experiment to provide an in-depth insight into the capacity of ACPs in (i) treating residual biofilm and (ii) preventing bacterial recolonisation.
Materials and methods: In the first stage, we used a titanium LISS plate coated with hand-mixed PALACOS with vancomycin (PAL-V) for temporary internal fixation combined with commercially prepared COPAL with gentamicin and vancomycin (COP-GV) to fill the segmental defect. In the second stage, the non-union was treated with double-plate fixation and bone grafting.
A Kirby–Bauer agar disc diffusion assay was performed to determine the antimicrobial activity of both ACPs and a drug-release assay to measure antibiotic release over time. A biofilm killing assay was also carried out to determine if the antibiotic released was able to reduce or eradicate biofilm of the patient's MRSA strain.
Results: At one-year follow-up, there was complete bone-bridging across the previous non-union. The patient was pain-free and ambulatory without need for further surgery. Both ACPs with COP-GV and PAL-V exerted an antimicrobial effect against the MRSA strain with peak concentrations of antibiotic released within the first 24 hours. Concentrations released from COP-GV in the first 24 hours in vitro caused a 7.7-fold log reduction of colony-forming units (CFU) in the biofilm. At day 50, both COP-GV and PAL-V still released concentrations of antibiotic above the respective minimal inhibitory concentrations (MIC), likely contributing to the positive clinical outcome.
Conclusion: The use of an ACP provides stability and infection control in the clinical scenario of an infected non-union. This is confirmed in vitro where the release of antibiotics from ACPs is characterised by an early burst followed by a prolonged sustained release above the MIC until 50 days. The burst release from COP-GV reduces CFU in the biofilm and prevents early recolonisation through synergistic activity of the released vancomycin and gentamicin.
Clinical significance: An antibiotic-impregnated cement-coated plate is a useful addition to the surgeon's armamentarium to provide temporary internal fixation without the disadvantages of external fixation and contribute to infection control in an infected non-union.
Brinker MR, Trivedi A, O’Connor DP. Debilitating effects of femoral nonunion on health-related quality of life. J Orthop Trauma 2017;31(2):e37–e42. DOI: 10.1097/BOT.0000000000000736.
Iliaens J, Onsea J, Hoekstra H, et al. Fracture-related infection in long bone fractures: A comprehensive analysis of the economic impact and influence on quality of life. Injury 2021;52(11):3344–3349. DOI: 10.1016/j.injury.2021.08.023.
Bauer T, Klouche S, Grimaud O, et al. Treatment of infected non-unions of the femur and tibia in a French referral center for complex bone and joint infections: Outcomes of 55 patients after 2 to 11 years. Orthop Traumatol Surg Res 2018;104(1):137–145. DOI: 10.1016/j.otsr.2017.10.014.
Metsemakers W-J, Morgenstern M, Senneville E, et al. General treatment principles for fracture-related infection: Recommendations from an international expert group. Arch Orthop Trauma Surg 2020;140(8):1013–1027. DOI: 10.1007/s00402-019-03287-4.
Depypere M, Morgenstern M, Kuehl R, et al. Pathogenesis and management of fracture-related infection. Clin Microbiol Infect 2020;26(5):572–578. DOI: 10.1016/j.cmi.2019.08.006.
Morelli I, Drago L, George DA, et al. Masquelet technique: Myth or reality? A systematic review and meta-analysis. Injury 2016;47(Suppl 6):S68–S76. DOI: 10.1016/S0020-1383(16)30842-7.
Janssen SJ, Kloen P. Supercutaneous locking compression plate in the treatment of infected non-union and open fracture of the leg. Arch Orthop Trauma Surg 2022;142(11):3201–3211. DOI: 10.1007/s00402-021-04104-7.
Kloen P. Supercutaneous plating: Use of a locking compression plate as an external fixator. J Orthop Trauma 2009;23(1):72–75. DOI: 10.1097/BOT.0b013e31818f8de4.
Hake ME, Young H, Hak DJ, et al. Local antibiotic therapy strategies in orthopaedic trauma: Practical tips and tricks and review of the literature. Injury 2015;46(8):1447–1456. DOI: 10.1016/j.injury.2015.05.008.
Thonse R, Conway J. Antibiotic cement-coated interlocking nail for the treatment of infected nonunions and segmental bone defects. J Orthop Trauma 2007;21(4):258–268. DOI: 10.1097/BOT.0b013e31803ea9e6.
Ismat A, Walter N, Baertl S, et al. Antibiotic cement coating in orthopedic surgery: A systematic review of reported clinical techniques. J Orthop Traumatol 2021;22(1):56. DOI: 10.1186/s10195-021-00614-7.
Liporace FA, Yoon RS, Frank MA, et al. Use of an “antibiotic plate” for infected periprosthetic fracture in total hip arthroplasty. J Orthop Trauma 2012;26(3):e18–e23. DOI: 10.1097/BOT.0b013e318216dd60.
Wang X, Wang S, Xu J, et al. Antibiotic cement plate composite structure internal fixation after debridement of bone infection. Sci Rep 2021;11(1):16921. DOI: 10.1038/s41598-021-96522-1.
Jia C, Wang X, Yu S, et al. An antibiotic cement-coated locking plate as a temporary fixation for treatment of infected bone defects: A new method of stabilization. J Orthop Surg Res 2020;15(1):44. DOI: 10.1186/s13018-020-1574-2.
Scolaro JA, Mehta S. Stabilisation of infected peri-articular nonunions with an antibiotic impregnated cement coated locking plate: Technique and indications. Injury 2016;47(6):1353–1356. DOI: 10.1016/j.injury.2016.03.010.
Yu X, Wu H, Li J, et al. Antibiotic cement-coated locking plate as a temporary internal fixator for femoral osteomyelitis defects. Int Orthop 2017;41(9):1851–1857. DOI: 10.1007/s00264-016-3258-4.
Johnson JP, Cohen EM, Antoci V. Treatment of a periprosthetic femur fracture around an antibiotic spacer with revision and an antibiotic plate. Arthroplast Today 2019;5(4):401–406. DOI: 10.1016/j.artd.2019.09.007.
Keller DM, Pizzo RA, Patel JN, et al. Use of antibiotic-cement coated locking plates in the setting of periprosthetic infection and infected nonunion. Injury 2022;53(7):2567–2572. DOI: 10.1016/j.injury.2022.03.040.
Boelens JJ, Tan WF, Dankert J, et al. Antibacterial activity of antibiotic-soaked polyvinylpyrrolidone-grafted silicon elastomer hydrocephalus shunts. J Antimicrob Chemother 2000;45(2):221–224. DOI: 10.1093/jac/45.2.221.
Neut D, Dijkstra RJB, Thompson JI, et al. A gentamicin-releasing coating for cementless hip prostheses—Longitudinal evaluation of efficacy using in vitro bio-optical imaging and its wide-spectrum antibacterial efficacy. J Biomed Mater Res Part A 2012;100A(12):3220–3226. DOI: 10.1002/jbm.a.34258.
Conway JD, Hlad LM, Bark SE. Antibiotic cement-coated plates for management of infected fractures. Am J Orthop (Belle Mead NJ) 2015;44(2):E49–E53. PMID: 25658083.
Walter N, Rupp M, Krückel J, et al. Individual and commercially available antimicrobial coatings for intramedullary nails for the treatment of infected long bone non-unions – A systematic review. Injury 2022;53(Suppl 3):S74–S80. DOI: 10.1016/j.injury.2022.05.008.
Moojen DJ, Hentenaar B, Charles Vogely H, et al. In vitro release of antibiotics from commercial PMMA beads and articulating hip spacers. J Arthroplasty 2008;23(8):1152–1156. DOI: 10.1016/j.arth.2007.08.020.
Wall V, Nguyen T-H, Nguyen N, et al. Controlling antibiotic release from polymethylmethacrylate bone cement. Biomedicines 2021;9(1):26. DOI: 10.3390/biomedicines9010026.
Frew NM, Cannon T, Nichol T, et al. Comparison of the elution properties of commercially available gentamicin and bone cement containing vancomycin with ‘home-made’ preparations. Bone Joint J 2017;99-B(1):73–77. DOI: 10.1302/0301-620X.99B1.BJJ-2016-0566.R1.
Boelch SP, Jordan MC, Arnholdt J, et al. Loading with vancomycin does not decrease gentamicin elution in gentamicin premixed bone cement. J Mater Sci Mater Med 2017;28(7):104. DOI: 10.1007/s10856-017-5915-6.
Chang YH, Tai CL, Hsu HY, et al. Liquid antibiotics in bone cement: an effective way to improve the efficiency of antibiotic release in antibiotic loaded bone cement. Bone Joint Res 2014;3(8):246–251.
Jain AK, Sinha S. Infected nonunion of the long bones. Clin Orthop Relat Res 2005;(431):57–65. DOI: 10.1097/01.blo.0000152868.29134.92.
Lee CG, Fu YC, Wang CH. Simulation of gentamicin delivery for the local treatment of osteomyelitis. Biotechnol Bioeng 2005;91(5):622–635. DOI: 10.1002/bit.20538.
Silveira AC, Sambrano GE, Paim TG, et al. Is prediffusion test an alternative to improve accuracy in screening hVISA strains and to detect susceptibility to glycopeptides/lipopeptides? Diagn Microbiol Infect Dis 2014;79(4):401–404. DOI: 10.1016/j.diagmicrobio.2014.04.008.
von Eiff C, Lindner N, Proctor RA, et al. Development of gentamicin-resistant small colony variants of S. aureus after implantation of gentamicin chains in osteomyelitis as a possible cause of recurrence. Z Orthop Ihre Grenzgeb 1998;136(3):268–271. PMID: 9736990.
Neut D, van de Belt H, Stokroos I, et al. Biomaterial-associated infection of gentamicin-loaded PMMA beads in orthopaedic revision surgery. J Antimicrob Chemother 2001;47(6):885–891. DOI: 10.1093/jac/47.6.885.