Articles | Volume 10, issue 4
https://doi.org/10.5194/jbji-10-327-2025
© Author(s) 2025. This work is distributed under
the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
https://doi.org/10.5194/jbji-10-327-2025
© Author(s) 2025. This work is distributed under
the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
CarboCell G/C offers high and prolonged concentrations of gentamicin and clindamycin in bone tissue following intraosseous injection
Mads Kristian Duborg Mikkelsen
CORRESPONDING AUTHOR
Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Andrea René Jørgensen
Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark
Niranjan G. Kotla
Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark
Maiken Stilling
Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, Denmark
Maria Bech Damsgaard
Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Christoph Crocoll
Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark
Michal Poborsky
Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark
Hans Christian Rasmussen
Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark
Jonas Rosager Henriksen
Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark
Anders Elias Hansen
Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark
Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, Denmark
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Louise Kruse Jensen, Thomas Bjarnsholt, Hans Gottlieb, and Mats Bue
J. Bone Joint Infect., 10, 1–5, https://doi.org/10.5194/jbji-10-1-2025, https://doi.org/10.5194/jbji-10-1-2025, 2025
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To improve the existing knowledge and treatment of bone and joint infections, it is essential to unite medical disciplines and bridge the gap between basic and clinical sciences. In 2018, the Centrum fOr translational Medicine on Bone and joint INfEctions (COMBINE) was created to facilitate collaboration among Danish scientists and researchers dedicated to bone and joint infection research. This paper aims to share the COMBINE approach and values.
Rehne Lessmann Hansen, Mats Bue, Anna Bertoli Borgognoni, and Klaus Kjær Petersen
J. Bone Joint Infect., 7, 35–42, https://doi.org/10.5194/jbji-7-35-2022, https://doi.org/10.5194/jbji-7-35-2022, 2022
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This study consists of 26 patients with infection of the pubic symphysis. The authors believe that by drawing awareness to this condition patients may be diagnosed and undergo surgery faster; 21 of the patients had pelvic surgery before onset of pubic infection. The diagnostic delay was between 1 and 12 months. All patients underwent surgical debridement and received a minimum of 6 weeks antibiotic treatment; 23 patients had postoperative pain relief and 19 patients were ambulant without aids.
Mats Bue, Arnar Óskar Bjarnason, Jan Duedal Rölfing, Karina Larsen, and Juozas Petruskevicius
J. Bone Joint Infect., 6, 135–140, https://doi.org/10.5194/jbji-6-135-2021, https://doi.org/10.5194/jbji-6-135-2021, 2021
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In order to monitor pin site infections, facilitate communication between team members, and assist treatment decision-making, we aimed to develop a registration tool. The present pilot study evaluates the feasibility of a prospective registration procedure for reporting, evaluating, and monitoring of pin site infections in 39 trauma, limb deformity, and bone infection patients with external ring fixation.
Josephine Olsen Kipp, Pelle Hanberg, Josefine Slater, Line Møller Nielsen, Stig Storgaard Jakobsen, Maiken Stilling, and Mats Bue
J. Bone Joint Infect., 6, 99–106, https://doi.org/10.5194/jbji-6-99-2021, https://doi.org/10.5194/jbji-6-99-2021, 2021
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To evaluate bone and tissue concentrations following intraosseous vancomycin administration, eight pigs were injected with 500 mg vancomycin into the tibia followed by a 12 h sampling period. This provided high concentrations in the tibia bone nearby the injection site the entire period, though with a wide range of peak concentration. The systemic absorption was high and immediate, thus mirroring an intravenous administration. Low mean concentrations were found in adjacent tissue compartments.
Cited articles
Buchholz, H. W., Elson, R. A., and Heinert, K.: Antibiotic-loaded acrylic cement: current concepts, Clin. Orthop. Relat. Res., 190, 96–108, 1984.
Bue, M., Hanberg, P., Koch, J., Jensen, L. K., Lundorff, M., Aalbaek, B., Jensen, H. E., Søballe, K., and Tøttrup, M.: Single-dose bone pharmacokinetics of vancomycin in a porcine implant-associated osteomyelitis model, J. Orthop. Res., 36, 1093–1098, https://doi.org/10.1002/jor.23776, 2018.
Dudareva, M., Kümin, M., Vach, W., Kaier, K., Ferguson, J., McNally, M., and Scarborough, M.: Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO): a randomised controlled open-label non-inferiority trial of duration of systemic antibiotics in adults with orthopaedic infection treated operatively with local antibiotic therapy, Trials, 20, 693, https://doi.org/10.1186/s13063-019-3832-3, 2019.
Ensing, G. T., van Horn, J. R., van der Mei, H. C., Busscher, H. J., and Neut, D.: Copal bone cement is more effective in preventing biofilm formation than Palacos R-G, Clin. Orthop. Relat. Res., 466, 1492–1498, https://doi.org/10.1007/s11999-008-0203-x, 2008.
EUCAST: Data from the EUCAST MIC distribution website, https://mic.eucast.org, last access: 14 April 2025.
Fuglsang-Madsen, A. J., Henriksen, N. L., Chávez, E. S., Kvich, L. A., Birch, J. K. M., Hartmann, K. T., Eriksen, T., Bjarnsholt, T., Gottlieb, H., Andresen, T. L., Jensen, L. K., Henriksen, J. R., and Hansen, A. E.: Eradication of Staphylococcus aureus in Implant-Associated Osteomyelitis by an Injectable In Situ-Forming Depot Antibiotics Delivery System, J. Infect. Dis., 230, 614–623, https://doi.org/10.1093/infdis/jiae139, 2024.
Hansen, A. E., Henriksen, J. R., Jølck, R. I., Fliedner, F. P., Bruun, L. M., Scherman, J., Jensen, A. I., Munck Af Rosenschöld, P., Moorman, L., Kurbegovic, S., de Blanck, S. R., Larsen, K. R., Clementsen, P. F., Christensen, A. N., Clausen, M. H., Wang, W., Kempen, P., Christensen, M., Viby, N. E., Persson, G., Larsen, R., Conradsen, K., McEvoy, F. J., Kjaer, A., Eriksen, T., and Andresen, T. L.: Multimodal soft tissue markers for bridging high-resolution diagnostic imaging with therapeutic intervention, Sci. Adv., 6, eabb5353, https://doi.org/10.1126/sciadv.abb5353, 2020.
Henriksen, N. L., Serrano-Chávez, E., Fuglsang-Madsen, A., Jensen, L. K., Gottlieb, H., Bue, M., Andresen, T. L., Henriksen, J. R., and Hansen, A. E.: Gentamicin and clindamycin antibiotic-eluting depot technology eradicates S. aureus in an implant-associated osteomyelitis pig model without systemic antibiotics, Antimicrob. Agents Chemother, 68, e0069124, https://doi.org/10.1128/aac.00691-24, 2024.
Kalbas, Y., Klingebiel, F., and Pape, H. C.: Antibiotic coated nails: Rationale, development, indications and outcomes, J. Orthop. Surg.-Hong K., 30, 10225536221118521, https://doi.org/10.1177/10225536221118521, 2022.
McNally, M. A., Ferguson, J. Y., Scarborough, M., Ramsden, A., Stubbs, D. A., and Atkins, B. L.: Mid- to long-term results of single-stage surgery for patients with chronic osteomyelitis using a bioabsorbable gentamicin-loaded ceramic carrier, Bone Joint J., 104-b, 1095–1100, https://doi.org/10.1302/0301-620x.104b9.Bjj-2022-0396.R1, 2022.
Mereddy, P., Nallamilli, S. R., Gowda, V. P., Kasha, S., Godey, S. K., Nallamilli, R. R., Gprk, R., and Meda, V. G. R.: The use of Stimulan in bone and joint infections, Bone Jt. Open, 4, 516–522, https://doi.org/10.1302/2633-1462.47.Bjo-2023-0036.R1, 2023.
Metsemakers, W. J., Fragomen, A. T., Moriarty, T. F., Morgenstern, M., Egol, K. A., Zalavras, C., Obremskey, W. T., Raschke, M., and McNally, M. A.: Evidence-Based Recommendations for Local Antimicrobial Strategies and Dead Space Management in Fracture-Related Infection, J. Orthop. Trauma, 34, 18–29, https://doi.org/10.1097/bot.0000000000001615, 2020.
Moore, A. J., Blom, A. W., Whitehouse, M. R., and Gooberman-Hill, R.: Deep prosthetic joint infection: a qualitative study of the impact on patients and their experiences of revision surgery, BMJ Open, 5, e009495, https://doi.org/10.1136/bmjopen-2015-009495, 2015.
Morgenstern, M., Vallejo, A., McNally, M. A., Moriarty, T. F., Ferguson, J. Y., Nijs, S., and Metsemakers, W. J.: The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis, Bone Joint Res., 7, 447–456, https://doi.org/10.1302/2046-3758.77.Bjr-2018-0043.R1, 2018.
Neut, D., de Groot, E. P., Kowalski, R. S., van Horn, J. R., van der Mei, H. C., and Busscher, H. J.: Gentamicin-loaded bone cement with clindamycin or fusidic acid added: biofilm formation and antibiotic release, J. Biomed. Mater. Res. A, 73, 165–170, https://doi.org/10.1002/jbm.a.30253, 2005.
Olsen Kipp, J., Hanberg, P., Slater, J., Møller Nielsen, L., Storgaard Jakobsen, S., Stilling, M., and Bue, M.: Vancomycin bone and tissue concentrations following tibial intraosseous administration – evaluated in a porcine model, J. Bone Joint Infect., 6, 99–106, https://doi.org/10.5194/jbji-6-99-2021, 2021.
Saeed, K., McLaren, A. C., Schwarz, E. M., Antoci, V., Arnold, W. V., Chen, A. F., Clauss, M., Esteban, J., Gant, V., Hendershot, E., Hickok, N., Higuera, C. A., Coraça-Huber, D. C., Choe, H., Jennings, J. A., Joshi, M., Li, W. T., Noble, P. C., Phillips, K. S., Pottinger, P. S., Restrepo, C., Rohde, H., Schaer, T. P., Shen, H., Smeltzer, M., Stoodley, P., Webb, J. C. J., and Witsø, E.: 2018 international consensus meeting on musculoskeletal infection: Summary from the biofilm workgroup and consensus on biofilm related musculoskeletal infections, J. Orthop. Res., 37, 1007–1017, https://doi.org/10.1002/jor.24229, 2019.
Sigmund, I. K., Palmer, A. J. R., Hotchen, A. J., McNally, M. A., Young, B. C., Alvand, A., Taylor, A., and Kendrick, B. J. L.: The use of antibiotic-loaded calcium sulphate beads in debridement, antibiotics, and implant retention (DAIR) for periprosthetic infections: a retrospective comparative cohort on outcome, Acta Orthop., 95, 707–714, https://doi.org/10.2340/17453674.2024.42360, 2024.
Tøttrup, M., Bue, M., Koch, J., Jensen, L. K., Hanberg, P., Aalbæk, B., Fuursted, K., Jensen, H. E., and Søballe, K.: Effects of Implant-Associated Osteomyelitis on Cefuroxime Bone Pharmacokinetics: Assessment in a Porcine Model, J. Bone Joint Surg. Am., 98, 363–369, https://doi.org/10.2106/jbjs.O.00550, 2016.
Young, B. C., Dudareva, M., Vicentine, M. P., Hotchen, A. J., Ferguson, J., and McNally, M.: Microbial Persistence, Replacement and Local Antimicrobial Therapy in Recurrent Bone and Joint Infection, Antibiotics (Basel), 12, 708, https://doi.org/10.3390/antibiotics12040708, 2023.
Zaborowska, M., Tillander, J., Brånemark, R., Hagberg, L., Thomsen, P., and Trobos, M.: Biofilm formation and antimicrobial susceptibility of staphylococci and enterococci from osteomyelitis associated with percutaneous orthopaedic implants, J. Biomed. Mater. Res. B Appl. Biomater., 105, 2630–2640, https://doi.org/10.1002/jbm.b.33803, 2017.
Zmistowski, B., Karam, J. A., Durinka, J. B., Casper, D. S., and Parvizi, J.: Periprosthetic joint infection increases the risk of one-year mortality, J. Bone Joint Surg. Am., 95, 2177–2184, https://doi.org/10.2106/jbjs.L.00789, 2013.
Short summary
In recent decades, there has been a growing emphasis on the use of local antibiotics in orthopaedic surgery, but development of new technologies has been limited. In this study we observe that a 1.5 mL injection of the novel technology CarboCell G/C into the bone provides very high levels of the antibiotics gentamicin and clindamycin in bones, with almost no spill to the bloodstream. These findings bolster the prospect of new and improved technologies for combatting orthopaedic infections.
In recent decades, there has been a growing emphasis on the use of local antibiotics in...