Skip to main content
Top
Published in: Journal of Orthopaedic Surgery and Research 1/2018

Open Access 01-12-2018 | Research article

Double-layered antibiotic-loaded cement spacer as a novel alternative for managing periprosthetic joint infection: an in vitro study

Authors: Shinsuke Ikeda, Katsufumi Uchiyama, Yojiro Minegishi, Keiko Ohno, Masaki Nakamura, Kazuhiro Yoshida, Kensuke Fukushima, Naonobu Takahira, Masashi Takaso

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2018

Login to get access

Abstract

Background

Previous studies comparing antibiotic-loaded calcium phosphate cement to polymethylmethacrylate cement reported that although the former has higher elution volumes over a longer period, it is mechanically weak when used alone. To counter this problem, a double-layered antibiotic-loaded cement spacer in which calcium phosphate cement is coated with polymethylmethacrylate cement was created.

Methods

In this study, we compared the double-layered spacer to the polymethylmethacrylate cement spacer in terms of eluent antibiotic concentration, bioactivity against methicillin-resistant Staphylococcus aureus, and mechanical strength. Double-layered and polymethylmethacrylate cement spacers that were loaded with vancomycin (VCM) were prepared and immersed in phosphate buffer for 84 days. To facilitate VCM elution from calcium phosphate cores in double-layered spacers, we also drilled multiple holes into the calcium phosphate layer from the spacer surface.

Results

We found that VCM concentrations in double-layered spacer eluents were higher than those in polymethylmethacrylate cement spacer eluents. The double-layered spacer also had higher bioactivity than the polymethylmethacrylate cement spacer. Although the polymethylmethacrylate cement spacer eluent lost the ability to inhibit bacterial growth on day 56, the double-layered spacer eluent maintained this ability for the duration of our study. Finally, the double-layered spacer retained high mechanical strength throughout the study period.

Conclusions

The beneficial biomechanical and drug-eluting properties of the double-layered spacer might qualify it to serve as a promising biomaterial that could be used for managing periprosthetic joint infections.
Literature
1.
go back to reference Widmer AF. New developments in diagnosis and treatment of infection in orthopedic implants. Clin Infect Dis. 2001;33:S94–106.CrossRef Widmer AF. New developments in diagnosis and treatment of infection in orthopedic implants. Clin Infect Dis. 2001;33:S94–106.CrossRef
2.
go back to reference Berbari E, Hanssen A. Risk factors for prosthetic joint infection: case-control study. Clin Infect Dis. 1998;27:1247–54.CrossRef Berbari E, Hanssen A. Risk factors for prosthetic joint infection: case-control study. Clin Infect Dis. 1998;27:1247–54.CrossRef
3.
go back to reference Sperling JW, Kozak TK, Hanssen AD, Cofield RH. Infection after shoulder arthroplasty. Clin Orthop Relat Res. 2001;382:206–16.CrossRef Sperling JW, Kozak TK, Hanssen AD, Cofield RH. Infection after shoulder arthroplasty. Clin Orthop Relat Res. 2001;382:206–16.CrossRef
4.
go back to reference Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the infectious diseases Society of America. Clin Infect Dis. 2013;56:1–25.CrossRef Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the infectious diseases Society of America. Clin Infect Dis. 2013;56:1–25.CrossRef
5.
go back to reference Davis JS. Management of bone and joint infections due to Staphylococcus aureus. Intern Med J. 2005;35(Suppl 2):S79–96.CrossRef Davis JS. Management of bone and joint infections due to Staphylococcus aureus. Intern Med J. 2005;35(Suppl 2):S79–96.CrossRef
6.
go back to reference Takesue Y, Kusachi S, Mikamo H, Sato J, Kawabata R, Ohge H, et al. Antimicrobial susceptibility of pathogens isolated from surgical site infections in Japan: comparison of data from nationwide surveillance studies conducted in 2010 and 2014 e 2015. J Infect Chemother. 2017;23:1–10.CrossRef Takesue Y, Kusachi S, Mikamo H, Sato J, Kawabata R, Ohge H, et al. Antimicrobial susceptibility of pathogens isolated from surgical site infections in Japan: comparison of data from nationwide surveillance studies conducted in 2010 and 2014 e 2015. J Infect Chemother. 2017;23:1–10.CrossRef
7.
go back to reference Citak LM, Levicoff E, Meani E, Motta F, Pena OR, Wellman SS. Spacers. J Orthop Res. 2014;32:S120–9.CrossRef Citak LM, Levicoff E, Meani E, Motta F, Pena OR, Wellman SS. Spacers. J Orthop Res. 2014;32:S120–9.CrossRef
8.
go back to reference Kisanuki O, Yajima H, Umeda T, Takakura Y. Experimental study of calcium phosphate cement impregnated with dideoxy-kanamycin B. J Orthop Sci. 2007;12:281–8.CrossRef Kisanuki O, Yajima H, Umeda T, Takakura Y. Experimental study of calcium phosphate cement impregnated with dideoxy-kanamycin B. J Orthop Sci. 2007;12:281–8.CrossRef
9.
go back to reference Sasaki T, Ishibashi Y, Katano H, Nagumo A, Toh S. In vitro elution of vancomycin from calcium phosphate cement. J Arthroplast. 2005;20:1055–9.CrossRef Sasaki T, Ishibashi Y, Katano H, Nagumo A, Toh S. In vitro elution of vancomycin from calcium phosphate cement. J Arthroplast. 2005;20:1055–9.CrossRef
10.
go back to reference Uchiyama K, Takahira N, Fukushima K, Moriya M, Yamamoto T, Minegishi Y, et al. Two-stage revision total hip arthroplasty for periprosthetic infections using antibiotic-impregnated cement spacers of various types and materials. Sci World J. 2013;2013:4–8. Uchiyama K, Takahira N, Fukushima K, Moriya M, Yamamoto T, Minegishi Y, et al. Two-stage revision total hip arthroplasty for periprosthetic infections using antibiotic-impregnated cement spacers of various types and materials. Sci World J. 2013;2013:4–8.
11.
go back to reference Kaku N, Tabata T, Tsumura H. Mechanical evaluation of hip cement spacer reinforcement with stainless steel Kirschner wires, titanium and carbon rods, and stainless steel mesh. Eur J Orthop Surg Traumatol. 2015;25:489–96.CrossRef Kaku N, Tabata T, Tsumura H. Mechanical evaluation of hip cement spacer reinforcement with stainless steel Kirschner wires, titanium and carbon rods, and stainless steel mesh. Eur J Orthop Surg Traumatol. 2015;25:489–96.CrossRef
12.
go back to reference Kuroda M, Ohta T, Uchiyama I, Baba T, Yuzawa H, Kobayashi I, et al. Whole genome sequencing of methicillin-resistant Staphylococcus aureus. Lancet. 2001;357:1225–40.CrossRef Kuroda M, Ohta T, Uchiyama I, Baba T, Yuzawa H, Kobayashi I, et al. Whole genome sequencing of methicillin-resistant Staphylococcus aureus. Lancet. 2001;357:1225–40.CrossRef
13.
go back to reference Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; twenty-second informational supplement. Wayne, PA: Clinical and Laboratory Standards Institute; 2013. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; twenty-second informational supplement. Wayne, PA: Clinical and Laboratory Standards Institute; 2013.
14.
go back to reference Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48:452–8.CrossRef Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48:452–8.CrossRef
15.
go back to reference DiCicco M, Duong T, Chu A, Jansen SA. Tobramycin and gentamycin elution analysis between two in situ polymerizable orthopedic composites. J Biomed Mater Res B Appl Biomater. 2003;65:137–49.CrossRef DiCicco M, Duong T, Chu A, Jansen SA. Tobramycin and gentamycin elution analysis between two in situ polymerizable orthopedic composites. J Biomed Mater Res B Appl Biomater. 2003;65:137–49.CrossRef
16.
go back to reference Jiranek WA. Antibiotic-loaded bone cement for infection prophylaxis in total joint replacement. J Bone Jt Surg. 2006;88:2487–500.CrossRef Jiranek WA. Antibiotic-loaded bone cement for infection prophylaxis in total joint replacement. J Bone Jt Surg. 2006;88:2487–500.CrossRef
17.
go back to reference Kanellakopoulou K, Tsaganos T, Athanassiou K, Koutoukas P, Raftogiannis M, Skiadas I, et al. Comparative elution of moxifloxacin from Norian skeletal repair system and acrylic bone cement: an in vitro study. Int J Antimicrob Agents. 2006;28:217–20.CrossRef Kanellakopoulou K, Tsaganos T, Athanassiou K, Koutoukas P, Raftogiannis M, Skiadas I, et al. Comparative elution of moxifloxacin from Norian skeletal repair system and acrylic bone cement: an in vitro study. Int J Antimicrob Agents. 2006;28:217–20.CrossRef
18.
go back to reference Urabe K, Naruse K, Hattori H, Hirano M, Uchida K, Onuma K, et al. In vitro comparison of elution characteristics of vancomycin from calcium phosphate cement and polymethylmethacrylate. J Orthop Sci. 2009;14:784–93.CrossRef Urabe K, Naruse K, Hattori H, Hirano M, Uchida K, Onuma K, et al. In vitro comparison of elution characteristics of vancomycin from calcium phosphate cement and polymethylmethacrylate. J Orthop Sci. 2009;14:784–93.CrossRef
19.
go back to reference Van De Belt H, Neut D, Uges DRA, Schenk W, Van Horn JR, Van Der Mei HC, et al. Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release. Biomaterials. 2000;21:1981–7.CrossRef Van De Belt H, Neut D, Uges DRA, Schenk W, Van Horn JR, Van Der Mei HC, et al. Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release. Biomaterials. 2000;21:1981–7.CrossRef
20.
go back to reference Anagnostakos K, Kelm J. Enhancement of antibiotic elution from acrylic bone cement. J Biomed Mater Res B Appl Biomater. 2009;90B:467–75.CrossRef Anagnostakos K, Kelm J. Enhancement of antibiotic elution from acrylic bone cement. J Biomed Mater Res B Appl Biomater. 2009;90B:467–75.CrossRef
21.
go back to reference Slane JA, Vivanco JF, Rose WE, Squire MW, Ploeg HL. The influence of low concentrations of a water soluble poragen on the material properties, antibiotic release, and biofilm inhibition of an acrylic bone cement. Mater Sci Eng C. 2014;42:168–76.CrossRef Slane JA, Vivanco JF, Rose WE, Squire MW, Ploeg HL. The influence of low concentrations of a water soluble poragen on the material properties, antibiotic release, and biofilm inhibition of an acrylic bone cement. Mater Sci Eng C. 2014;42:168–76.CrossRef
22.
go back to reference Popieniek PH, Pratt RF. Kinetics and mechanism of binding of specific peptides to vancomycin and other glycopeptide antibiotics. J Am Chem Soc. 1991;113:2264–70.CrossRef Popieniek PH, Pratt RF. Kinetics and mechanism of binding of specific peptides to vancomycin and other glycopeptide antibiotics. J Am Chem Soc. 1991;113:2264–70.CrossRef
23.
go back to reference Nishimura S, Tsurumoto T, Yonekura A, Adachi K, Shindo H. Antimicrobial susceptibility of Staphylococcus aureus and Staphylococcus epidermidis biofilms isolated from infected total hip arthroplasty cases. J Orthop Sci. 2006;11:46–50.CrossRef Nishimura S, Tsurumoto T, Yonekura A, Adachi K, Shindo H. Antimicrobial susceptibility of Staphylococcus aureus and Staphylococcus epidermidis biofilms isolated from infected total hip arthroplasty cases. J Orthop Sci. 2006;11:46–50.CrossRef
24.
go back to reference Rybak M, Lomaestro B, Rotschafer JC, Moellering R, Craig W, Billeter M, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Heal Pharm. 2009;66:82–98.CrossRef Rybak M, Lomaestro B, Rotschafer JC, Moellering R, Craig W, Billeter M, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Heal Pharm. 2009;66:82–98.CrossRef
25.
go back to reference Steinkraus G, White R, Friedrich L. Vancomycin MIC creep in non-vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-susceptible clinical methicillin-resistant S. aureus (MRSA) blood isolates from 2001-05. J Antimicrob Chemother. 2007;60:788–94.CrossRef Steinkraus G, White R, Friedrich L. Vancomycin MIC creep in non-vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-susceptible clinical methicillin-resistant S. aureus (MRSA) blood isolates from 2001-05. J Antimicrob Chemother. 2007;60:788–94.CrossRef
26.
go back to reference Wang G, Hindler JF, Ward KW, Bruckner DA. Increased vancomycin MICs for Staphylococcus aureus clinical isolates from a university hospital during a 5-year period. J Clin Microbiol. 2006;44:3883–6.CrossRef Wang G, Hindler JF, Ward KW, Bruckner DA. Increased vancomycin MICs for Staphylococcus aureus clinical isolates from a university hospital during a 5-year period. J Clin Microbiol. 2006;44:3883–6.CrossRef
27.
go back to reference Kehrmann J, Kaase M, Szabados F, Gatermann SG, Buer J, Rath PM, et al. Vancomycin MIC creep in MRSA blood culture isolates from Germany: a regional problem? Eur J Clin Microbiol Infect Dis. 2011;30:677–83.CrossRef Kehrmann J, Kaase M, Szabados F, Gatermann SG, Buer J, Rath PM, et al. Vancomycin MIC creep in MRSA blood culture isolates from Germany: a regional problem? Eur J Clin Microbiol Infect Dis. 2011;30:677–83.CrossRef
28.
go back to reference Ambard AJ, Mueninghoff L. Calcium phosphate cement: review of mechanical and biological properties. J Prosthodont. 2006;15:321–8.CrossRef Ambard AJ, Mueninghoff L. Calcium phosphate cement: review of mechanical and biological properties. J Prosthodont. 2006;15:321–8.CrossRef
29.
go back to reference Bergmann G, Graichen F, Rohlmann A. Hip joint loading during walking and running, measured in two patients. J Biomech. 1993;26:969–90.CrossRef Bergmann G, Graichen F, Rohlmann A. Hip joint loading during walking and running, measured in two patients. J Biomech. 1993;26:969–90.CrossRef
30.
go back to reference Jung J. Complications after spacer implantation in the treatment of hip joint infections. Int J Med Sci. 2009;6:265.CrossRef Jung J. Complications after spacer implantation in the treatment of hip joint infections. Int J Med Sci. 2009;6:265.CrossRef
31.
go back to reference Lewis G, Janna S, Bhattaram A. Influence of the method of blending an antibiotic powder with an acrylic bone cement powder on physical, mechanical, and thermal properties of the cured cement. Biomaterials. 2005;26:4317–25.CrossRef Lewis G, Janna S, Bhattaram A. Influence of the method of blending an antibiotic powder with an acrylic bone cement powder on physical, mechanical, and thermal properties of the cured cement. Biomaterials. 2005;26:4317–25.CrossRef
Metadata
Title
Double-layered antibiotic-loaded cement spacer as a novel alternative for managing periprosthetic joint infection: an in vitro study
Authors
Shinsuke Ikeda
Katsufumi Uchiyama
Yojiro Minegishi
Keiko Ohno
Masaki Nakamura
Kazuhiro Yoshida
Kensuke Fukushima
Naonobu Takahira
Masashi Takaso
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2018
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-018-1033-5

Other articles of this Issue 1/2018

Journal of Orthopaedic Surgery and Research 1/2018 Go to the issue