Combination of modified mixing technique and low frequency ultrasound to control the elution profile of vancomycin-loaded acrylic bone cement

Objectives The objective of this study was to determine if combining variations in mixing technique of antibiotic-impregnated polymethylmethacrylate (PMMA) cement with low frequency ultrasound (LFUS) improves antibiotic elution during the initial high phase (Phase I) and subsequent low phase (Phase II) while not diminishing mechanical strength. Methods Three batches of vancomycin-loaded PMMA were prepared with different mixing techniques: a standard technique; a delayed technique; and a control without antibiotic. Daily elution samples were analysed using flow injection analysis (FIA). Beginning in Phase II, samples from each mix group were selected randomly to undergo either five, 15, 45, or 0 minutes of LFUS treatment. Elution amounts between LFUS treatments were analysed. Following Phase II, compression testing was done to quantify strength. A-priori t-tests and univariate ANOVAs were used to compare elution and mechanical test results between the two mix groups and the control group. Results The delayed technique showed a significant increase in elution on day one compared with the standard mix technique (p < 0.001). The transition point from Phase I to Phase II occurred on day ten. LFUS treatments significantly increased elution amounts for all groups above control. Delayed technique resulted in significantly higher elution amounts for the five-minute- (p = 0.004) and 45-minute- (p < 0.001) duration groups compared with standard technique. Additionally, the correlations between LFUS duration and total elution amount for both mix techniques were significant (p = 0.03). Both antibiotic-impregnated groups exhibited a significant decrease in offset yield stress compared with the control group (p < 0.001), however, their lower 95% confidence intervals were all above the 70 MPa limit defined by International Standards Organization (ISO) 5833-2 reference standard for acrylic bone cement. Conclusion The combination of a delayed mix technique with LFUS treatments provides a reasonable means for increasing both short- and long-term antibiotic elution without affecting mechanical strength. Cite this article: Dr. T. McIff. Combination of modified mixing technique and low frequency ultrasound to control the elution profile of vancomycin-loaded acrylic bone cement. Bone Joint Res 2016;5:26–32. DOI: 10.1302/2046-3758.52.2000412

[1]  K. Urabe,et al.  In vitro comparison of elution characteristics of vancomycin from calcium phosphate cement and polymethylmethacrylate , 2009, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[2]  J. Parvizi,et al.  Two-stage Exchange Arthroplasty for Infected Total Knee Arthroplasty: Predictors of Failure , 2011, Clinical orthopaedics and related research.

[3]  S. Joo,et al.  CuO nanosheets-enhanced flow-injection chemiluminescence system for determination of vancomycin in water, pharmaceutical and human serum. , 2014, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[4]  A. Mikos,et al.  Antibiotic-releasing porous polymethylmethacrylate/gelatin/antibiotic constructs for craniofacial tissue engineering. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[5]  M. Hawn,et al.  Surgical Site Infection After Arthroplasty: Comparative Effectiveness of Prophylactic Antibiotics: Do Surgical Care Improvement Project Guidelines Need to Be Updated? , 2014, The Journal of bone and joint surgery. American volume.

[6]  R. McLemore,et al.  Strength of Antimicrobial Bone Cement Decreases with Increased Poragen Fraction , 2010, Clinical orthopaedics and related research.

[7]  J. V. van Horn,et al.  The influence of ultrasound on the release of gentamicin from antibiotic-loaded acrylic beads and bone cements. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[8]  Hao-bo Wu,et al.  Effect of Delayed Pulsed-Wave Ultrasound on Local Pharmacokinetics and Pharmacodynamics of Vancomycin-Loaded Acrylic Bone Cement In Vivo , 2007, Antimicrobial Agents and Chemotherapy.

[9]  D. Wininger,et al.  Antibiotic-impregnated cement and beads for orthopedic infections , 1996, Antimicrobial agents and chemotherapy.

[10]  Christopher L. Stewart,et al.  Effect of an ultrasonic device on temperatures generated in bone and on bone-cement structure. , 1993, The Journal of arthroplasty.

[11]  M. Bostrom,et al.  Evaluation and Management of Periprosthetic Joint Infection–an International, Multicenter Study , 2014, HSS Journal ®.

[12]  A. Benini,et al.  Different microbial biofilm formation on polymethylmethacrylate (PMMA) bone cement loaded with gentamicin and vancomycin. , 2011, Anaerobe.

[13]  B. Masri,et al.  Amphotericin B-loaded bone cement to treat osteomyelitis caused by Candida albicans. , 2001, Canadian journal of surgery. Journal canadien de chirurgie.

[14]  T. McIff,et al.  Compression strength and porosity of single-antibiotic cement vacuum-mixed with vancomycin. , 2010, The Journal of arthroplasty.

[15]  J. Ticó,et al.  Application of an experimental design for the optimization and validation of a new HPLC method for the determination of vancomycin in an extemporaneous ophthalmic solution. , 2008, Journal of chromatographic science.

[16]  B. Masri,et al.  Elution characteristics of vancomycin and tobramycin combined in acrylic bone-cement. , 1996, The Journal of arthroplasty.

[17]  J. Xu,et al.  Intermittent watt-level ultrasonication facilitates vancomycin release from therapeutic acrylic bone cement. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[18]  Nitesh Gahlot,et al.  Prosthetic joint infection following total hip replacement: results of one-stage versus two-stage exchange , 2014, International Orthopaedics.

[19]  J R van Horn,et al.  Backgrounds of antibiotic-loaded bone cement and prosthesis-related infection. , 2004, Biomaterials.

[20]  W. Zimmerli,et al.  Prosthetic-joint infections. , 2004, The New England journal of medicine.

[21]  W. Li,et al.  Preparation and characterization of PHBV microsphere/45S5 bioactive glass composite scaffolds with vancomycin releasing function. , 2014, Materials science & engineering. C, Materials for biological applications.

[22]  T. Peel,et al.  Prosthetic Joint Infections , 2018, Springer International Publishing.

[23]  J. Kelm,et al.  Classification of hip joint infections , 2009, International journal of medical sciences.

[24]  C. Grimsrud,et al.  The in vitro elution characteristics of antifungal-loaded PMMA bone cement and calcium sulfate bone substitute. , 2011, Orthopedics.

[25]  K. Saleh,et al.  Treating periprosthetic joint infections as biofilms: key diagnosis and management strategies. , 2015, Diagnostic microbiology and infectious disease.

[26]  A. Lilikakis,et al.  The effect of vancomycin addition to the compression strength of antibiotic-loaded bone cements , 2009, International Orthopaedics.

[27]  M. J. Hall,et al.  National Hospital Discharge Survey, 2005 , 2007 .

[28]  Antonios G Mikos,et al.  Antibiotic-releasing porous polymethylmethacrylate constructs for osseous space maintenance and infection control. , 2010, Biomaterials.

[29]  D. Musher,et al.  Elution of vancomycin, daptomycin, and amikacin from acrylic bone cement. , 1991, Clinical orthopaedics and related research.

[30]  G. Schwantzer,et al.  Prosthetic joint infection following total hip replacement: results of one-stage versus two-stage exchange , 2014, International Orthopaedics.

[31]  T. McIff,et al.  Increasing the elution of vancomycin from high-dose antibiotic-loaded bone cement: a novel preparation technique. , 2012, The Journal of bone and joint surgery. American volume.