Articles | Volume 11, issue 1
https://doi.org/10.5194/jbji-11-95-2026
© Author(s) 2026. 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-11-95-2026
© Author(s) 2026. This work is distributed under
the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
Original full-length article
| 
10 Feb 2026
Original full-length article |
| 10 Feb 2026
| 10 Feb 2026
Safety of locally applied antibiotics in orthopaedic trauma surgery: descriptive results from a prospective cohort study
Niels Vanvelk
Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
Esther M. M. Van Lieshout
Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
Leendert H. T. Nugteren
Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
A. Cornelis Plaisier
Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
Rosalya Van der Pot
Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
Corine Bethlehem
Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
Willem-Jan Metsemakers
Department of Trauma Surgery, University Hospitals Leuven, Leuven, Belgium
Department of Development and Regeneration, KU Leuven, Leuven, Belgium
William T. Obremskey
Department of Orthopaedic Surgery and Rehabilitation, Vanderbilt University Medical Center, Nashville, TN, USA
Michael H. J. Verhofstad
CORRESPONDING AUTHOR
Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
Related authors
Niels Vanvelk, Esther M. M. Van Lieshout, Jolien Onsea, Jonathan Sliepen, Geertje Govaert, Frank F. A. IJpma, Melissa Depypere, Jamie Ferguson, Martin McNally, William T. Obremskey, Charalampos Zalavras, Michael H. J. Verhofstad, and Willem-Jan Metsemakers
J. Bone Joint Infect., 8, 133–142, https://doi.org/10.5194/jbji-8-133-2023, https://doi.org/10.5194/jbji-8-133-2023, 2023
Short summary
Short summary
This international retrospective cohort study displays the diagnostic characteristics of 609 patients who were treated for fracture-related infection (FRI). Clinical confirmatory criteria were present in 77% of patients. In the remaining patients, the decision to operatively collect deep tissue cultures had to be based on a set of suggestive criteria. The combined use of these suggestive criteria should guide treating physicians in the management pathway of FRI.
Laura Bessems, Jolien Onsea, Baixing Chen, Marjan Wouthuyzen-Bakker, Irene K. Sigmund, Tristan Ferry, Richard Kuehl, Martin Clauss, Alex Soriano, Ricardo Sousa, Annette Schuermans, and Willem-Jan Metsemakers
J. Bone Joint Infect., 10, 489–500, https://doi.org/10.5194/jbji-10-489-2025, https://doi.org/10.5194/jbji-10-489-2025, 2025
Short summary
Short summary
Isolation of patients with musculoskeletal infections in orthopedic care is controversial. Evidence supports selective isolation for certain resistant pathogens but not for non-resistant pathogens, nor does it support the routine use of septic wards. Effective infection control depends on hospital-wide strategies and adherence to standard precautions, with specialized centres offering better care than dedicated isolation units.
Jonathan Sliepen, Michelle A. S. Buijs, Jolien Onsea, Geertje A. M. Govaert, Frank F. A. IJpma, Jean-Paul P. M. de Vries, Bart C. H. Van der Wal, Charalampos Zalavras, and Willem-Jan Metsemakers
J. Bone Joint Infect., 10, 347–361, https://doi.org/10.5194/jbji-10-347-2025, https://doi.org/10.5194/jbji-10-347-2025, 2025
Short summary
Short summary
This review assessed the effectiveness of single- and two-stage procedures for treating long-bone fracture-related infections, focusing on unhealed fractures without critical-sized bone defects. A total of 35 studies with 985 patients showed bone-healing rates of 80% for single-stage procedures and 77% for two-stage procedures. Infection eradication rates were 87% for single-stage approaches and 81% for two-stage approaches. The current evidence is inconclusive and lacks sufficient data to favor either approach.
Ann-Sophie Jacob, Jolien Onsea, Laura Bessems, Pauline Spoormans, Georges Vles, Willem-Jan Metsemakers, Sien Ombelet, and Melissa Depypere
J. Bone Joint Infect., 10, 317–326, https://doi.org/10.5194/jbji-10-317-2025, https://doi.org/10.5194/jbji-10-317-2025, 2025
Short summary
Short summary
Fracture-related infections (FRIs) and periprosthetic joint infections (PJIs) fail to recover pathogens, posing a diagnostic challenge and impacting treatment. This new method involves homogenising biopsies with beads to release bacteria, followed by inoculation in blood culture bottles using an automated system. This technique shows similar sensitivity to conventional methods, with improved specificity and faster pathogen detection. To date, no other studies have reported an optimized method for incubating biopsies from patients with FRIs.
Irene K. Sigmund, Marjan Wouthuyzen-Bakker, Tristan Ferry, Willem-Jan Metsemakers, Martin Clauss, Alex Soriano, Rihard Trebse, and Ricardo Sousa
J. Bone Joint Infect., 10, 139–142, https://doi.org/10.5194/jbji-10-139-2025, https://doi.org/10.5194/jbji-10-139-2025, 2025
Short summary
Short summary
This is a summary of our position paper on debridement, antimicrobial therapy, and implant retention (DAIR) procedures as a curative treatment strategy for acute periprosthetic hip and knee infections. It includes the defined indications as well as the contraindications of DAIR procedures when eradication/cure is intended, based on the currently available literature.
Irene K. Sigmund, Tristan Ferry, Ricardo Sousa, Alex Soriano, Willem-Jan Metsemakers, Martin Clauss, Rihard Trebse, and Marjan Wouthuyzen-Bakker
J. Bone Joint Infect., 10, 101–138, https://doi.org/10.5194/jbji-10-101-2025, https://doi.org/10.5194/jbji-10-101-2025, 2025
Short summary
Short summary
In this paper, we discuss the most relevant factors influencing the outcome and define indications, contraindications, and risk factors of a DAIR procedure based on the currently available literature. Furthermore, we discuss the surgical technique in combination with systemic antimicrobial therapy in patients undergoing a DAIR procedure.
Baixing Chen, T. Fintan Moriarty, Hans Steenackers, Georges F. Vles, Jolien Onsea, Thijs Vackier, Isabel Spriet, Rob Lavigne, R. Geoff Richards, and Willem-Jan Metsemakers
J. Bone Joint Infect., 9, 249–260, https://doi.org/10.5194/jbji-9-249-2024, https://doi.org/10.5194/jbji-9-249-2024, 2024
Short summary
Short summary
Our research explores natural antimicrobials to combat orthopedic-device-related infections, a challenging issue due to antibiotic resistance. We reviewed agents from bacteria, fungi, viruses, animals, plants and minerals, evaluating their effectiveness and synergy with traditional antibiotics. Our findings suggest these natural alternatives could revolutionize infection management in orthopedic patients, offering new hope for reducing antibiotic resistance and improving treatment outcomes.
Fred Ruythooren, Stijn Ghijselings, Melissa Depypere, Willem-Jan Metsemakers, Liesbet Henckaerts, Nathalie Noppe, and Georges Vles
J. Bone Joint Infect., 9, 167–171, https://doi.org/10.5194/jbji-9-167-2024, https://doi.org/10.5194/jbji-9-167-2024, 2024
Short summary
Short summary
The article examines a unique case of Ureaplasma urealyticum causing osteomyelitis in the greater trochanter of a 26-year-old male treated with ocrelizumab for multiple sclerosis. It emphasizes the necessity of a multidisciplinary approach and advanced PCR diagnostics to manage such rare opportunistic infections effectively, highlighting the challenges faced due to the immunosuppressive nature of monoclonal antibody therapies of this kind.
Jordi Cools, Stijn Ghijselings, Fred Ruythooren, Sander Jentjens, Nathalie Noppe, Willem-Jan Metsemakers, and Georges Vles
J. Bone Joint Infect., 9, 27–35, https://doi.org/10.5194/jbji-9-27-2024, https://doi.org/10.5194/jbji-9-27-2024, 2024
Short summary
Short summary
Septic arthritis (SA) of the native adult hip is a rare orthopaedic emergency. To date, the role of advanced imaging has been confined to supporting or opposing diagnosis; however, implications for surgical decision-making and outcomes have not yet been established. We found that extra-articular abscesses are present in two out of three patients and require varying anatomical approaches. Therefore, we recommend routinely performing advanced imaging in all adults with SA of the native hip joint.
Fred Ruythooren, Stijn Ghijselings, Jordi Cools, Melissa Depypere, Paul De Munter, Willem-Jan Metsemakers, and Georges Vles
J. Bone Joint Infect., 8, 209–218, https://doi.org/10.5194/jbji-8-209-2023, https://doi.org/10.5194/jbji-8-209-2023, 2023
Short summary
Short summary
A total of 41 patients who underwent surgical treatment for septic arthritis (SA) of the native hip were studied. We show that patients with SA of the native hip can be divided in three distinct clinical subgroups based on route of infection. Route of infection is directly related to the chance of femoral head preservation and should, therefore, be the basis for decision-making. Only patients with blood-borne infections in an undamaged hip had a reasonable chance of femoral head preservation.
Niels Vanvelk, Esther M. M. Van Lieshout, Jolien Onsea, Jonathan Sliepen, Geertje Govaert, Frank F. A. IJpma, Melissa Depypere, Jamie Ferguson, Martin McNally, William T. Obremskey, Charalampos Zalavras, Michael H. J. Verhofstad, and Willem-Jan Metsemakers
J. Bone Joint Infect., 8, 133–142, https://doi.org/10.5194/jbji-8-133-2023, https://doi.org/10.5194/jbji-8-133-2023, 2023
Short summary
Short summary
This international retrospective cohort study displays the diagnostic characteristics of 609 patients who were treated for fracture-related infection (FRI). Clinical confirmatory criteria were present in 77% of patients. In the remaining patients, the decision to operatively collect deep tissue cultures had to be based on a set of suggestive criteria. The combined use of these suggestive criteria should guide treating physicians in the management pathway of FRI.
Cited articles
Anagnostakos, K. and Meyer, C.: Antibiotic Elution from Hip and Knee Acrylic Bone Cement Spacers: A Systematic Review, Biomed. Res. Int., 2017, 4657874, https://doi.org/10.1155/2017/4657874, 2017.
Bezstarosti, H., Van Lieshout, E. M. M., Van den Hurk, M. J. B., Kortram, K., Oprel, P., Koch, B. C. P., Croughs, P. D., and Verhofstad, M. H. J.: In Vitro Elution of Gentamicin from CERAMENT(R) G Has an Antimicrobial Effect on Bacteria With Various Levels of Gentamicin Resistance Found in Fracture-related Infection, Clin. Orthop. Relat. Res., 482, 885–891, https://doi.org/10.1097/CORR.0000000000002975, 2024.
Buckman, S. A., Forrester, J. D., Bessoff, K. E., Parli, S. E., Evans, H. L., and Huston, J. M.: Surgical Infection Society Guidelines: 2022 Updated Guidelines for Antibiotic Use in Open Extremity Fractures, Surg. Infect. (Larchmt), 23, 817–828, https://doi.org/10.1089/sur.2022.206, 2022.
Chaudhry, Y. P., LaGreca, M., Hayes, H., Papadelis, E., Rao, S. S., and Amin, R.: Acute kidney injury in the context of staged revision arthroplasty and the use of antibiotic-laden cement spacers: a systematic review, J. Orthop. Surg. Res., 18, 340, https://doi.org/10.1186/s13018-023-03809-2, 2023.
de Klaver, P. A., Hendriks, J. G., van Onzenoort, H. A., Schreurs, B. W., Touw, D. J., and Derijks, L. J.: Gentamicin serum concentrations in patients with gentamicin-PMMA beads for infected hip joints: a prospective observational cohort study, Ther. Drug Monit., 34, 67–71, https://doi.org/10.1097/FTD.0b013e31823d7b89, 2012.
Depypere, M., Kuehl, R., Metsemakers, W. J., Senneville, E., McNally, M. A., Obremskey, W. T., Zimmerli, W., Atkins, B. L., Trampuz, A., and Fracture-Related Infection Consensus Group: Recommendations for Systemic Antimicrobial Therapy in Fracture-Related Infection: A Consensus From an International Expert Group, J. Orthop. Trauma, 34, 30–41, https://doi.org/10.1097/BOT.0000000000001626, 2020.
Duey, R. E., Chong, A. C., McQueen, D. A., Womack, J. L., Song, Z., Steinberger, T. A., and Wooley, P. H.: Mechanical properties and elution characteristics of polymethylmethacrylate bone cement impregnated with antibiotics for various surface area and volume constructs, Iowa Orthop. J., 32, 104–115, 2012.
Flores, M. J., Brown, K. E., Morshed, S., and Shearer, D. W.: Evidence for Local Antibiotics in the Prevention of Infection in Orthopaedic Trauma, J. Clin. Med., 11, https://doi.org/10.3390/jcm11247461, 2022.
Haidari, S., Buijs, M. A. S., Plate, J. D. J., Zomer, J. J., Ijpma, F. F. A., Hietbrink, F., and Govaert, G. A. M.: Costs of fracture-related infection: the impact on direct hospital costs and healthcare utilisation, Eur. J. Trauma Emerg. Surg., 50, 1701–1707, https://doi.org/10.1007/s00068-024-02497-9, 2024.
Iliaens, J., Onsea, J., Hoekstra, H., Nijs, S., Peetermans, W. E., and Metsemakers, W. J.: Fracture-related infection in long bone fractures: A comprehensive analysis of the economic impact and influence on quality of life, Injury, 52, 3344–3349, https://doi.org/10.1016/j.injury.2021.08.023, 2021.
Janssen, D. M. C., Willems, P., Geurts, J., and Arts, C. J. J.: Antibiotic release from PMMA spacers and PMMA beads measured with ELISA: Assessment of in vitro samples and drain fluid samples of patients, J. Orthop. Res., 41, 1831–1839, https://doi.org/10.1002/jor.25510, 2023.
Johnson, J. D., Nessler, J. M., Horazdovsky, R. D., Vang, S., Thomas, A. J., and Marston, S. B.: Serum and Wound Vancomycin Levels After Intrawound Administration in Primary Total Joint Arthroplasty, J. Arthroplasty, 32, 924–928, https://doi.org/10.1016/j.arth.2015.10.015, 2017.
Leehey, D. J., Braun, B. I., Tholl, D. A., Chung, L. S., Gross, C. A., Roback, J. A., and Lentino, J. R.: Can pharmacokinetic dosing decrease nephrotoxicity associated with aminoglycoside therapy, J. Am. Soc. Nephrol., 4, 81–90, https://doi.org/10.1681/ASN.V4181, 1993.
Lopez-Novoa, J. M., Quiros, Y., Vicente, L., Morales, A. I., and Lopez-Hernandez, F. J.: New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view, Kidney Int., 79, 33–45, https://doi.org/10.1038/ki.2010.337, 2011.
Luu, A., Syed, F., Raman, G., Bhalla, A., Muldoon, E., Hadley, S., Smith, E., and Rao, M.: Two-stage arthroplasty for prosthetic joint infection: a systematic review of acute kidney injury, systemic toxicity and infection control, J. Arthroplasty, 28, 1490–1498, https://doi.org/10.1016/j.arth.2013.02.035, 2013.
Maruo, A., Oda, T., Mineo, R., Miya, H., Muratsu, H., Fukui, T., Oe, K., Kuroda, R., and Niikura, T.: Continuous local antibiotic perfusion: A treatment strategy that allows implant retention in fracture-related infections, J. Orthop. Surg. (Hong Kong), 30, https://doi.org/10.1177/10225536221111902, 2022.
Meeker, D. G., Cooper, K. B., Renard, R. L., Mears, S. C., Smeltzer, M. S., and Barnes, C. L.: Comparative Study of Antibiotic Elution Profiles From Alternative Formulations of Polymethylmethacrylate Bone Cement, J. Arthroplasty, 34, 1458–1461, https://doi.org/10.1016/j.arth.2019.03.008, 2019.
Metsemakers, W. J., Emanuel, N., Cohen, O., Reichart, M., Potapova, I., Schmid, T., Segal, D., Riool, M., Kwakman, P. H., de Boer, L., de Breij, A., Nibbering, P. H., Richards, R. G., Zaat, S. A., and Moriarty, T. F.: A doxycycline-loaded polymer-lipid encapsulation matrix coating for the prevention of implant-related osteomyelitis due to doxycycline-resistant methicillin-resistant Staphylococcus aureus, J. Control Release, 209, 47–56, https://doi.org/10.1016/j.jconrel.2015.04.022, 2015.
Metsemakers, W. J., Smeets, B., Nijs, S., and Hoekstra, H.: Infection after fracture fixation of the tibia: Analysis of healthcare utilization and related costs, Injury, 48, 1204–1210, https://doi.org/10.1016/j.injury.2017.03.030, 2017.
Metsemakers, W. J., Morgenstern, M., McNally, M. A., Moriarty, T. F., McFadyen, I., Scarborough, M., Athanasou, N. A., Ochsner, P. E., Kuehl, R., Raschke, M., Borens, O., Xie, Z., Velkes, S., Hungerer, S., Kates, S. L., Zalavras, C., Giannoudis, P. V., Richards, R. G., and Verhofstad, M. H. J.: Fracture-related infection: A consensus on definition from an international expert group, Injury, 49, 505–510, https://doi.org/10.1016/j.injury.2017.08.040, 2018.
Metsemakers, W. J., Fragomen, A. T., Moriarty, T. F., Morgenstern, M., Egol, K. A., Zalavras, C., Obremskey, W. T., Raschke, M., McNally, M. A., and Fracture-Related Infection Consensus Group: 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.
Meyer, J., Piller, G., Spiegel, C. A., Hetzel, S., and Squire, M.: Vacuum-mixing significantly changes antibiotic elution characteristics of commercially available antibiotic-impregnated bone cements, J. Bone Joint Surg. Am., 93, 2049–2056, https://doi.org/10.2106/JBJS.J.01777, 2011.
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.
Nelson, C. L., Griffin, F. M., Harrison, B. H., and Cooper, R. E.: In vitro elution characteristics of commercially and noncommercially prepared antibiotic PMMA beads, Clin. Orthop. Relat. Res., 303–309, 1992.
Obremskey, W. T., Metsemakers, W. J., Schlatterer, D. R., Tetsworth, K., Egol, K., Kates, S., McNally, M., and ICM Orthopaedic Trauma Work Group: Musculoskeletal Infection in Orthopaedic Trauma: Assessment of the 2018 International Consensus Meeting on Musculoskeletal Infection, J. Bone Joint Surg. Am., 102, e44, https://doi.org/10.2106/JBJS.19.01070, 2020.
O'Hara, N. N., Carullo, J., Joshi, M., Banoub, M., Claeys, K. C., Sprague, S., Slobogean, G. P., O'Toole, R. V., and PREP-IT Investigators: Does cumulative topical antibiotic powder use increase the risk of drug induced acute kidney injury in fracture patients?, Bone Jt. Open, 3, 284–290, https://doi.org/10.1302/2633-1462.34.BJO-2022-0009.R1, 2022.
O'Toole, R. V., Degani, Y., Carlini, A. R., Castillo, R. C., O'Hara, N. N., Joshi, M., and METRC: Systemic Absorption and Nephrotoxicity Associated With Topical Vancomycin Powder for Fracture Surgery, J. Orthop. Trauma, 35, 29–34, https://doi.org/10.1097/BOT.0000000000001866, 2021.
Raveh, D., Kopyt, M., Hite, Y., Rudensky, B., Sonnenblick, M., and Yinnon, A. M.: Risk factors for nephrotoxicity in elderly patients receiving once-daily aminoglycosides, QJM, 95, 291–297, https://doi.org/10.1093/qjmed/95.5.291, 2002.
Sliepen, J., Corrigan, R. A., Dudareva, M., Wouthuyzen-Bakker, M., Rentenaar, R. J., Atkins, B. L., Govaert, G. A. M., McNally, M. A., and Ijpma, F. F. A.: Does the Use of Local Antibiotics Affect Clinical Outcome of Patients with Fracture-Related Infection?, Antibiotics (Basel), 11, https://doi.org/10.3390/antibiotics11101330, 2022.
Stravinskas, M., Horstmann, P., Ferguson, J., Hettwer, W., Nilsson, M., Tarasevicius, S., Petersen, M. M., McNally, M. A., and Lidgren, L.: Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies, Bone Joint Res., 5, 427–435, https://doi.org/10.1302/2046-3758.59.BJR-2016-0108.R1, 2016.
Thomas, T. L., Kothari, P. D., Baker, C. M., Tarabichi, S., Clark, S. C., and Goh, G. S.: High Incidence of Acute Kidney Injury Following Antibiotic-Loaded Spacer Insertion for Periprosthetic Joint Infection: An Updated Review of the Literature, J. Arthroplasty, 39, 549–558, https://doi.org/10.1016/j.arth.2023.08.055, 2024.
von Hertzberg-Boelch, S. P., Luedemann, M., Rudert, M., and Steinert, A. F.: PMMA Bone Cement: Antibiotic Elution and Mechanical Properties in the Context of Clinical Use, Biomedicines, 10, https://doi.org/10.3390/biomedicines10081830, 2022.
Wahlig, H., Dingeldein, E., Bergmann, R., and Reuss, K.: The release of gentamicin from polymethylmethacrylate beads. An experimental and pharmacokinetic study, J. Bone Joint Surg. Br., 60-B, 270–275, https://doi.org/10.1302/0301-620X.60B2.659478, 1978.
Walter, N., Rupp, M., Hierl, K., Pfeifer, C., Kerschbaum, M., Hinterberger, T., and Alt, V.: Long-term patient-related quality of life after fracture-related infections of the long bones, Bone Joint Res., 10, 321–327, https://doi.org/10.1302/2046-3758.105.BJR-2020-0532, 2021.
Wargo, K. A. and Edwards, J. D.: Aminoglycoside-induced nephrotoxicity, J. Pharm. Pract., 27, 573–577, https://doi.org/10.1177/0897190014546836, 2014.
Yamada, T., Fujii, S., Shigemi, A., and Takesue, Y.: A meta-analysis of the target trough concentration of gentamicin and amikacin for reducing the risk of nephrotoxicity, J. Infect. Chemother., 27, 256–261, https://doi.org/10.1016/j.jiac.2020.09.033, 2021.
Short summary
Although local antibiotic administration is used to prevent and treat fracture-related infections, concerns remain about systemic absorption and potential renal toxicity. This study assessed serum levels and renal function after local gentamicin or vancomycin use. Gentamicin exceeded the lower limit of quantification in 17% of cases but remained below toxic levels. Vancomycin was undetectable. These findings suggest that local antibiotic administration does not harm renal function.
Although local antibiotic administration is used to prevent and treat fracture-related...
