Elution of vancomycin and meropenem and their combinations from various bone cement materials

Introduction Saturation of bone defect filling materials with antibacterial agents is used for the treatment of patients with infectious bone complications and for their prevention.

The purpose of the work was to evaluate the elution rate of vancomycin and meropenem from bone cements based on polymethyl methacrylate and polyurethane polymers impregnated into the material in their combination.

Materials and methods In an in vitro study, a comparative analysis of the kinetics of vancomycin and meropenem release from two materials was performed that were based on polyurethane polymers (PU series) and polymethyl methacrylate (PMMA series). Antibiotics were added to the materials before their polymerization in the following proportions: group 1 — polymer : antibiotic 10 g : 1 g (0.5 g vancomycin + 0.5 g meropenem); group 2 — polymer : antibiotic 10 g : 0.5 g (0.25 g vancomycin + 0.25 g meropenem). Samples loaded with one antibiotic were used as a control: group 1v — polymer : antibiotic 10 g : vancomycin 0.5 g; group 1m — polymer : antibiotic 10 g : meropenem 0.5 g; group 2v — polymer: antibiotic 10 g: vancomycin 0.25 g; group 2m — polymer: antibiotic 10 g: meropenem 0.25 g.

Results Vancomycin elution from both PMMA- and PU-based materials loaded with a vancomycin+meropenem was greater in final volume and longer in time than from materials containing vancomycin alone. Conversely, meropenem release from PMMA and PU loaded with a vancomycin + meropenem mixture was less in volume than from the materials containing meropenem alone.

Discussion The use of a vancomycin-meropenem complex in bone cements reveals the following feature: meropenem promotes the release of vancomycin from the studied materials, while the elution of meropenem itself is reduced.

Conclusion Combining antibiotics for impregnation into materials for bone defect filling has an impact on the kinetics of antibiotics release, unlike the release kinetics of an antibiotic loaded into the material as monotherapy.

1. Sergeev GK, Kirpichov IV, Mal`chevskij VA et al. Modern strategies for the prevention and treatment of periimplant infection and postoperative osteomyelitis. Medical science and education of Ural. 2024;25(1):137-144. (In Russ.) doi: 10.36361/18148999_2024_25_1_137.

2. Wassif RK, Elkayal M, Shamma RN, Elkheshen SA. Recent advances in the local antibiotics delivery systems for management of osteomyelitis. Drug Deliv. 2021;28(1):2392-2414. doi: 10.1080/10717544.2021.1998246.

3. Xu T, Wu KL, Jie K. Comprehensive meta-analysis of antibiotic-impregnated bone cement versus plain bone cement in primary total knee arthroplasty for preventing periprosthetic joint infection. Chin J Traumatol. 2022;25(6):325-330. doi: 10.1016/j.cjtee.2022.06.001.

4. Cara A, Ferry T, Laurent F, Josse J. Prophylactic Antibiofilm Activity of Antibiotic-Loaded Bone Cements against GramNegative Bacteria. Antibiotics (Basel). 2022;11(2):137. doi: 10.3390/antibiotics11020137.

5. Dantas LR, Ortis GB, Suss PH, Tuon FF. Advances in Regenerative and Reconstructive Medicine in the Prevention and Treatment of Bone Infections. Biology (Basel). 2024;13(8):605. doi: 10.3390/biology13080605.

6. Jiang C, Zhu G, Liu Q. Current application and future perspectives of antimicrobial degradable bone substitutes for chronic osteomyelitis. Front Bioeng Biotechnol. 2024;12:1375266. doi: 10.3389/fbioe.2024.1375266.

7. Martínez-Moreno J, Merino V, Nácher A, et al. Antibiotic-loaded Bone Cement as Prophylaxis in Total Joint Replacement. Orthop Surg. 2017;9(4):331-341. doi: 10.1111/os.12351.

8. Stogov MV, Shastov AL, Kireeva EA, Tushina NV. Release of antibiotics from the materials for post-osteomyelitic bone defect filling. Genij Ortopedii. 2024;30(6):873-880. doi: 10.18019/1028-4427-2024-30-6-873-880.

9. Levack AE, Turajane K, Yang X, et al. Thermal Stability and in Vitro Elution Kinetics of Alternative Antibiotics in Polymethylmethacrylate (PMMA) Bone Cement. J Bone Joint Surg Am. 2021;103(18):1694-1704. doi: 10.2106/JBJS.20.00011.

10. Wang LH, Feng YD, Zhang XW, et al. Elution and Biomechanical Properties of Meropenem-Loaded Bone Cement. Orthop Surg. 2021;13(8):2417-2422. doi: 10.1111/os.13139.

11. Ermakov AM, Bogdanova NA, Matveeva EL, Gasanova AG. Analysis of the microbial landscape in patients with periprosthetic infection of the hip joint. Genij Ortopedii. 2025;31(3):307-313. doi: 10.18019/1028-4427-2025-31-3307-313.

12. Tsiskarashvili AV, Melikova RE, Nazarenko AG. Microbiological monitoring of major pathogens in infected long bone fractures treated with external osteosynthesis. N.N. Priorov Journal of Traumatology and Orthopedics. 2025;32(2):457475. (In Russ.) doi: 10.17816/vto655983.

13. Shipitsyna IV, Osipova EV. Role of anaerobic microflora in the etiology of chronic osteomyelitis. Russian Clinical Laboratory Diagnostics. 2024;69(2):92-96 (in Russ.) doi: 10.51620/0869-2084-2024-69-2-92-96.

14. 14. Sudnitsyn AS, Shastov AL, Klushin NM, Rashidov GKh. First experience with the use of a partially bioresorbable bone substitution material in a patient with 34-year old chronic osteomyelitis of the tibia. Genij Ortopedii. 2025;31(1):60-65. doi: 10.18019/1028-4427-2025-31-1-60-65.

15. Smith M, Roberts M, Al-Kassas R. Implantable drug delivery systems for the treatment of osteomyelitis. Drug Dev Ind Pharm. 2022;48(10):511-527. doi: 10.1080/03639045.2022.2135729.

16. Zegre M, Poljańska E, Caetano LA, et al. Research progress on biodegradable polymeric platforms for targeting antibiotics to the bone. Int J Pharm. 2023;648:123584. doi: 10.1016/j.ijpharm.2023.123584.

17. Lin H, Gao Z, Shan T, et al. A review on the promising antibacterial agents in bone cement-From past to current insights. J Orthop Surg Res. 2024;19(1):673. doi: 10.1186/s13018-024-05143-7.

18. Andollina A, Bertoni G, Zolezzi C, et al. Vancomycin and meropenem in acrylic cement: elution kinetics of in vitro bactericidal action. Chir Organi Mov. 2008;91(3):153-158. doi: 10.1007/s12306-007-0025-0.

19. Funk GA, Burkes JC, Cole KA, et al. Antibiotic Elution and Mechanical Strength of PMMA Bone Cement Loaded With Borate Bioactive Glass. J Bone Jt Infect. 2018;3(4):187-196. doi: 10.7150/jbji.27348.

20. Slane J, Gietman B, Squire M. Antibiotic elution from acrylic bone cement loaded with high doses of tobramycin and vancomycin. J Orthop Res. 2018;36(4):1078-1085. doi: 10.1002/jor.23722.

21. Hsieh PH, Tai CL, Lee PC, Chang YH. Liquid gentamicin and vancomycin in bone cement: a potentially more costeffective regimen. J Arthroplasty. 2009;24(1):125-130. doi: 10.1016/j.arth.2008.01.131.

22. Penner MJ, Masri BA, Duncan CP. Elution characteristics of vancomycin and tobramycin combined in acrylic bonecement. J Arthroplasty. 1996;11(8):939-944. doi: 10.1016/s0883-5403(96)80135-5.

23. Paz E, Sanz-Ruiz P, Abenojar J, et al. Evaluation of Elution and Mechanical Properties of High-Dose AntibioticLoaded Bone Cement: Comparative "In Vitro" Study of the Influence of Vancomycin and Cefazolin. J Arthroplasty. 2015;30(8):1423-1429. doi: 10.1016/j.arth.2015.02.040.

24. Fraval A, Zhou Y, Parvizi J. Antibiotic-loaded cement in total joint arthroplasty: a comprehensive review. Arch Orthop Trauma Surg. 2024;144(12):5165-5175. doi: 10.1007/s00402-024-05328-z.

25. von Hertzberg-Boelch SP, Luedemann M, Rudert M, Steinert AF. PMMA Bone Cement: Antibiotic Elution and Mechanical Properties in the Context of Clinical Use. Biomedicines. 2022;10(8):1830. doi: 10.3390/biomedicines10081830.

26. Coraça-Huber D, Humez M, Kühn KD. A Comparative Study of Extended Gentamicin and Tobramycin Release and Antibacterial Efficacy from Palacos and Simplex Acrylic Cements. Microorganisms. 2025;13(9):2174. doi: 10.3390/microorganisms13092174.

27. Si L, Zhang W, Jiang H, et al. Dual antibiotic PLGA microspheres for the treatment of traumatic osteomyelitis. Sci Rep. 2025;15(1):30694. doi: 10.1038/s41598-025-14824-0.

28. Dietz MJ, McGowan BM, Thomas DD, et al. Does Cement Viscosity Impact Antibiotic Elution and In Vitro Efficacy Against Common Prosthetic Joint Infection Pathogens? Clin Orthop Relat Res. 2025;483(3):488-497. doi: 10.1097/CORR.0000000000003272.

29. Bozhkova SA, Gadzhimagomedov MSh, Gordina EM et al. Experimental Validation of Antimicrobial Drug Combinations for Bone Cement Impregnation. Traumatology and Orthopedics of Russia. 2025;31(1):76-84. doi: 10.17816/2311-290517665.

30. Kazmi SAD, Soomro T, Soomro R, et al. Impact of Biofilms on Surface Properties of Polymethyl Methacrylate (PMMA) Resins. J Basic Microbiol. 2024;64(12):e2400460. doi: 10.1002/jobm.202400460.

31. Kreve S, Cândido Dos Reis A. Antibiofilm capacity of PMMA surfaces: A review of current knowledge. Microb Pathog. 2025;202:107426. doi: 10.1016/j.micpath.2025.107426.

32. Tseng TH, Chang CH, Chen CL, et al. A simple method to improve the antibiotic elution profiles from polymethylmethacrylate bone cement spacers by using rapid absorbable sutures. BMC Musculoskelet Disord. 2022;23(1):916. doi: 10.1186/s12891-022-05870-0.