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Published in: Journal of Orthopaedic Surgery and Research 1/2023

Open Access 01-12-2023 | Tigecycline | Research article

Comparison of antibacterial activity and biocompatibility of non-leaching nitrofuran bone cement loaded with vancomycin, gentamicin, and tigecycline

Authors: Zhe Gao, Yang Xu, Yuchen Kan, Hailong Li, Rui Guo, Luyang Han, Wenhan Bu, Jianjun Chu

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2023

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Abstract

Background

Non-leaching antibacterial bone cement can generate long-term antibacterial activity, it cannot treat serious infections that have occurred like antibiotic-loaded bone cement. Currently, the antibacterial activity and biocompatibility of non-leaching cement when loaded with antibiotics have yet to be determined.

Methods

Non-leaching antibacterial nitrofuran bone cement (NFBC) specimens were prepared with low-dose and high-dose antibiotics. The antibacterial activity and biocompatibility of NFBC loaded with vancomycin, gentamicin, and tigecycline were compared. The agar diffusion method was employed to observe the inhibition zone of the samples against two bacterial strains from day one to day seven. The CCK-8 assay and acute liver and kidney toxicity test were conducted to assess the effects of the samples on mouse embryo osteoblast precursor cells and C57 mice, respectively.

Results

Gentamicin-loaded cement exhibited the most potent antibacterial activity, effectively inhibiting both bacterial strains at a low dose. Tigecycline-loaded cement demonstrated superior biocompatibility, showing no acute liver and kidney toxicity in mice and minimal cytotoxicity to osteoblasts.

Conclusions

NFBC loaded with gentamicin, vancomycin, and tigecycline not only maintains sustained antibacterial activity but also exhibits excellent biocompatibility.
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Literature
1.
go back to reference Thomas B, Benedikt M, Alamri A, et al. The role of antibiotic-loaded bone cement in complicated knee arthroplasty: relevance of gentamicin allergy and benefit from revision surgery—a case control follow-up study and algorithmic approach. J Orthop Surg Res. 2020;15(1):319.CrossRefPubMedPubMedCentral Thomas B, Benedikt M, Alamri A, et al. The role of antibiotic-loaded bone cement in complicated knee arthroplasty: relevance of gentamicin allergy and benefit from revision surgery—a case control follow-up study and algorithmic approach. J Orthop Surg Res. 2020;15(1):319.CrossRefPubMedPubMedCentral
2.
go back to reference Al Thaher Y, Khalil R, Abdelghany S, Salem MS. Antimicrobial PMMA bone cement containing long releasing multi-walled carbon nanotubes. Nanomaterials. 2022;12(8):1381.CrossRefPubMedPubMedCentral Al Thaher Y, Khalil R, Abdelghany S, Salem MS. Antimicrobial PMMA bone cement containing long releasing multi-walled carbon nanotubes. Nanomaterials. 2022;12(8):1381.CrossRefPubMedPubMedCentral
3.
go back to reference Yang L, Yergeshov AA, Al-Thaher Y, et al. Nanocomposite orthopaedic bone cement combining long-acting dual antimicrobial drugs. Biomater Adv. 2023;153:213538.CrossRefPubMed Yang L, Yergeshov AA, Al-Thaher Y, et al. Nanocomposite orthopaedic bone cement combining long-acting dual antimicrobial drugs. Biomater Adv. 2023;153:213538.CrossRefPubMed
4.
go back to reference Al Thaher Y, Alfuqaha OA, Dweidari A. Health-related quality of life and outcome after total knee replacement: results from a cross-sectional survey in Jordan. Adv Orthop. 2021;2021:5506809.CrossRefPubMedPubMedCentral Al Thaher Y, Alfuqaha OA, Dweidari A. Health-related quality of life and outcome after total knee replacement: results from a cross-sectional survey in Jordan. Adv Orthop. 2021;2021:5506809.CrossRefPubMedPubMedCentral
5.
go back to reference Moojen DJ, Hentenaar B, Vogely HC, Verbout AJ, Castelein RM, Dhert WJ. In vitro release of antibiotics from commercial PMMA beads and articulating hip spacers. J Arthroplasty. 2008;23(8):1152–6.CrossRefPubMed Moojen DJ, Hentenaar B, Vogely HC, Verbout AJ, Castelein RM, Dhert WJ. In vitro release of antibiotics from commercial PMMA beads and articulating hip spacers. J Arthroplasty. 2008;23(8):1152–6.CrossRefPubMed
6.
go back to reference Cyphert EL, Learn GD, Hurley SK, et al. An additive to PMMA bone cement enables postimplantation drug refilling, broadens range of compatible antibiotics, and prolongs antimicrobial therapy. Adv Healthc Mater. 2018;7(21):e1800812.CrossRefPubMed Cyphert EL, Learn GD, Hurley SK, et al. An additive to PMMA bone cement enables postimplantation drug refilling, broadens range of compatible antibiotics, and prolongs antimicrobial therapy. Adv Healthc Mater. 2018;7(21):e1800812.CrossRefPubMed
7.
go back to reference Imazato S. Antibacterial properties of resin composites and dentin bonding systems. Dent Mater. 2003;19(6):449–57.CrossRefPubMed Imazato S. Antibacterial properties of resin composites and dentin bonding systems. Dent Mater. 2003;19(6):449–57.CrossRefPubMed
8.
go back to reference Almaroof A, Niazi SA, Rojo L, Mannocci F, Deb S. Influence of a polymerizable eugenol derivative on the antibacterial activity and wettability of a resin composite for intracanal post cementation and core build-up restoration. Dent Mater. 2016;32(7):929–39.CrossRefPubMed Almaroof A, Niazi SA, Rojo L, Mannocci F, Deb S. Influence of a polymerizable eugenol derivative on the antibacterial activity and wettability of a resin composite for intracanal post cementation and core build-up restoration. Dent Mater. 2016;32(7):929–39.CrossRefPubMed
10.
go back to reference Wright ZM, Pandit AM, Holt BD, et al. Therapeutic methacrylic comonomers for covalently controlled release from mechanically robust bone cement: kinetics and structure-function relationships. Macromolecules. 2019;52(10):3775–86.CrossRef Wright ZM, Pandit AM, Holt BD, et al. Therapeutic methacrylic comonomers for covalently controlled release from mechanically robust bone cement: kinetics and structure-function relationships. Macromolecules. 2019;52(10):3775–86.CrossRef
11.
go back to reference Wang H, Maeda T, Miyazaki T. Preparation of bioactive and antibacterial PMMA-based bone cement by modification with quaternary ammonium and alkoxysilane. J Biomater Appl. 2021;36(2):311–20.CrossRefPubMed Wang H, Maeda T, Miyazaki T. Preparation of bioactive and antibacterial PMMA-based bone cement by modification with quaternary ammonium and alkoxysilane. J Biomater Appl. 2021;36(2):311–20.CrossRefPubMed
12.
go back to reference Nadagouda MN, Vijayasarathy P, Sin A, et al. Antimicrobial activity of quaternary ammonium salts: structure-activity relationship. Med Chem Res. 2022;31(10):1663–78.CrossRef Nadagouda MN, Vijayasarathy P, Sin A, et al. Antimicrobial activity of quaternary ammonium salts: structure-activity relationship. Med Chem Res. 2022;31(10):1663–78.CrossRef
13.
14.
go back to reference Chen Y, Caneli G, Xie D. A PMMA bone cement with improved antibacterial function and flexural strength. J Biomater Sci Polym Ed. 2022;33(11):1398–414.CrossRefPubMed Chen Y, Caneli G, Xie D. A PMMA bone cement with improved antibacterial function and flexural strength. J Biomater Sci Polym Ed. 2022;33(11):1398–414.CrossRefPubMed
15.
go back to reference Zhu W, Liu F, Yu B, He J. Preparation of antibacterial acrylic bone cement with methacrylate derived from benzothiazole. J Mech Behav Biomed Mater. 2021;117:104403.CrossRefPubMed Zhu W, Liu F, Yu B, He J. Preparation of antibacterial acrylic bone cement with methacrylate derived from benzothiazole. J Mech Behav Biomed Mater. 2021;117:104403.CrossRefPubMed
16.
go back to reference Chu J, Li C, Guo J, et al. Preparation of new bio-based antibacterial acrylic bone cement via modification with a biofunctional monomer of nitrofurfuryl methacrylate. Polym Chem-UK. 2022;13(32):4675–83.CrossRef Chu J, Li C, Guo J, et al. Preparation of new bio-based antibacterial acrylic bone cement via modification with a biofunctional monomer of nitrofurfuryl methacrylate. Polym Chem-UK. 2022;13(32):4675–83.CrossRef
17.
go back to reference Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance. Lancet Infect Dis. 2001;1(3):147–55.CrossRefPubMed Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance. Lancet Infect Dis. 2001;1(3):147–55.CrossRefPubMed
18.
go back to reference Li B, Webster TJ. Bacteria antibiotic resistance: new challenges and opportunities for implant-associated orthopedic infections. J Orthop Res. 2018;36(1):22–32.CrossRefPubMed Li B, Webster TJ. Bacteria antibiotic resistance: new challenges and opportunities for implant-associated orthopedic infections. J Orthop Res. 2018;36(1):22–32.CrossRefPubMed
19.
go back to reference Terreni M, Taccani M, Pregnolato M. New antibiotics for multidrug-resistant bacterial strains: latest research developments and future perspectives. Molecules. 2021;26(9):2671.CrossRefPubMedPubMedCentral Terreni M, Taccani M, Pregnolato M. New antibiotics for multidrug-resistant bacterial strains: latest research developments and future perspectives. Molecules. 2021;26(9):2671.CrossRefPubMedPubMedCentral
20.
go back to reference Kasbekar N. Tigecycline: a new glycylcycline antimicrobial agent. Am J Health Syst Pharm. 2006;63(13):1235–43.CrossRefPubMed Kasbekar N. Tigecycline: a new glycylcycline antimicrobial agent. Am J Health Syst Pharm. 2006;63(13):1235–43.CrossRefPubMed
21.
go back to reference Yaghoubi S, Zekiy AO, Krutova M, et al. Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review. Eur J Clin Microbiol Infect Dis. 2022;41(7):1003–22.CrossRefPubMed Yaghoubi S, Zekiy AO, Krutova M, et al. Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review. Eur J Clin Microbiol Infect Dis. 2022;41(7):1003–22.CrossRefPubMed
22.
go back to reference Scott CP, Higham PA. Antibiotic bone cement for the treatment of Pseudomonas aeruginosa in joint arthroplasty: comparison of tobramycin and gentamicin-loaded cements. J Biomed Mater Res B Appl Biomater. 2003;64(2):94–8.CrossRefPubMed Scott CP, Higham PA. Antibiotic bone cement for the treatment of Pseudomonas aeruginosa in joint arthroplasty: comparison of tobramycin and gentamicin-loaded cements. J Biomed Mater Res B Appl Biomater. 2003;64(2):94–8.CrossRefPubMed
23.
go back to reference Ferraris S, Miola M, Bistolfi A, et al. In vitro comparison between commercially and manually mixed antibiotic-loaded bone cements. J Appl Biomater Biomech. 2010;8(3):166–74.PubMed Ferraris S, Miola M, Bistolfi A, et al. In vitro comparison between commercially and manually mixed antibiotic-loaded bone cements. J Appl Biomater Biomech. 2010;8(3):166–74.PubMed
24.
go back to reference Hudzicki J. Kirby-Bauer disk diffusion susceptibility test protocol. Am Soc Microbiol. 2009;15:55–63. Hudzicki J. Kirby-Bauer disk diffusion susceptibility test protocol. Am Soc Microbiol. 2009;15:55–63.
25.
go back to reference Jorgensen JH, Ferraro MJ. Antimicrobial susceptibility testing: a review of general principles and contemporary practices. Clin Infect Dis. 2009;49(11):1749–55.CrossRefPubMed Jorgensen JH, Ferraro MJ. Antimicrobial susceptibility testing: a review of general principles and contemporary practices. Clin Infect Dis. 2009;49(11):1749–55.CrossRefPubMed
26.
go back to reference Chang YH, Tai CL, Hsu HY, Hsieh PH, Lee MS, Ueng SW. Liquid antibiotics in bone cement: an effective way to improve the efficiency of antibiotic release in antibiotic loaded bone cement. Bone Jt Res. 2014;3(8):246–51.CrossRef Chang YH, Tai CL, Hsu HY, Hsieh PH, Lee MS, Ueng SW. Liquid antibiotics in bone cement: an effective way to improve the efficiency of antibiotic release in antibiotic loaded bone cement. Bone Jt Res. 2014;3(8):246–51.CrossRef
27.
go back to reference Wu S, Weir MD, Lei L, Liu J, Xu HHK. Novel nanographene oxide-calcium phosphate cement inhibits Enterococcus faecalis biofilm and supports dental pulp stem cells. J Orthop Surg Res. 2021;16(1):580.CrossRefPubMedPubMedCentral Wu S, Weir MD, Lei L, Liu J, Xu HHK. Novel nanographene oxide-calcium phosphate cement inhibits Enterococcus faecalis biofilm and supports dental pulp stem cells. J Orthop Surg Res. 2021;16(1):580.CrossRefPubMedPubMedCentral
28.
go back to reference Minelli EB, Caveiari C, Benini A. Release of antibiotics from polymethylmethacrylate cement. J Chemother. 2002;14(5):492–500.CrossRef Minelli EB, Caveiari C, Benini A. Release of antibiotics from polymethylmethacrylate cement. J Chemother. 2002;14(5):492–500.CrossRef
29.
go back to reference Klekamp J, Dawson JM, 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(3):339–46.CrossRefPubMed Klekamp J, Dawson JM, 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(3):339–46.CrossRefPubMed
30.
go back to reference Rozbruch SR, Weitzman AM, Watson JT, et al. Simultaneous treatment of tibial bone and soft-tissue defects with the Ilizarov method. J Orthop Trauma. 2006;20(3):197–205. Rozbruch SR, Weitzman AM, Watson JT, et al. Simultaneous treatment of tibial bone and soft-tissue defects with the Ilizarov method. J Orthop Trauma. 2006;20(3):197–205.
31.
go back to reference Isefuku S, Joyner CJ, Simpson AH. Gentamicin may have an adverse effect on osteogenesis. J Orthop Trauma. 2003;17(3):212–6.CrossRefPubMed Isefuku S, Joyner CJ, Simpson AH. Gentamicin may have an adverse effect on osteogenesis. J Orthop Trauma. 2003;17(3):212–6.CrossRefPubMed
32.
go back to reference Braun J, Eckes S, Rommens PM, Schmitz K, Nickel D, Ritz U. Toxic effect of vancomycin on viability and functionality of different cells involved in tissue regeneration. Antibiotics. 2020;9(5):238.CrossRefPubMedPubMedCentral Braun J, Eckes S, Rommens PM, Schmitz K, Nickel D, Ritz U. Toxic effect of vancomycin on viability and functionality of different cells involved in tissue regeneration. Antibiotics. 2020;9(5):238.CrossRefPubMedPubMedCentral
33.
go back to reference Wilcox MH. Efficacy of tigecycline in complicated skin and skin structure infections and complicated intra-abdominal infections. J Chemother. 2005;17(Suppl 1):23–9.CrossRefPubMed Wilcox MH. Efficacy of tigecycline in complicated skin and skin structure infections and complicated intra-abdominal infections. J Chemother. 2005;17(Suppl 1):23–9.CrossRefPubMed
Metadata
Title
Comparison of antibacterial activity and biocompatibility of non-leaching nitrofuran bone cement loaded with vancomycin, gentamicin, and tigecycline
Authors
Zhe Gao
Yang Xu
Yuchen Kan
Hailong Li
Rui Guo
Luyang Han
Wenhan Bu
Jianjun Chu
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2023
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-023-04055-2

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