Novel porcine model of implant‐associated osteomyelitis: A comprehensive analysis of local, regional, and systemic response

Jensen, Louise Kruse; Koch, Julian; Dich-Jorgensen, Kirstine; Aalbæk, Bent; Petersen, Andreas; Fuursted, Kurt; Bjarnsholt, Thomas; Kragh, Kasper Nørskov; Tøtterup, Mikkel; Bue, Mats; Hanberg, Pelle; Søballe, Kjeld; Heegaard, Peter M. H.; Jensen, Henrik Elvang

doi:10.1002/jor.23505

Cited by 34 publications

(85 citation statements)

References 32 publications

(79 reference statements)

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“…The present application of MD in a validated porcine osteomyelitis model therefore seems to be an important step toward understanding antimicrobial penetration in osteomyelitis. 27 In conclusion, Staphylococcus aureus implant associated osteomyelitis was found to significantly reduce vancomycin bone penetration, especially in the implant cavity. Consequently, it may be unsafe to rely solely on vancomycin therapy when treating acute osteomyelitis.…”

Section: Discussionmentioning

confidence: 83%

“…This resulted in acceptable mean RR values in the range of 21.3–40.0%. The present application of MD in a validated porcine osteomyelitis model therefore seems to be an important step toward understanding antimicrobial penetration in osteomyelitis …”

Section: Discussionmentioning

confidence: 99%

“…2013/15‐2934‐00946). The study was performed on a previously described osteomyelitis porcine model and analogous to a former study where cefuroxime was the study drug …”

Section: Methodsmentioning

confidence: 99%

“…The study was performed on a previously described osteomyelitis porcine model and analogous to a former study where cefuroxime was the study drug. 26,27 Overview Eight female pigs (Danish Landrace breed, weighing from 75 to 86 kg) were included in the study. They all went through two surgeries (day 0 and 5).…”

Section: Methodsmentioning

confidence: 99%

“…In recent years, the pharmacokinetic tool microdialysis (MD) has successfully been applied for sampling of various antimicrobials in drill holes in bone . The objective of this study was to evaluate the effect of a traumatically induced, implant‐associated acute osteomyelitis on vancomycin bone penetration in a porcine model …”

mentioning

confidence: 99%

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Single‐dose bone pharmacokinetics of vancomycin in a porcine implant‐associated osteomyelitis model

Bue

Hanberg

Koch

et al. 2017

Journal Orthopaedic Research

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The increasing incidence of orthopaedic methicillin-resistant Staphylococcus aureus (MRSA) infections represents a significant therapeutic challenge. Being effective against MRSA, the role of vancomycin may become more important in the orthopaedic setting in the years to come. Nonetheless, vancomycin bone and soft tissue penetration during infection remains unclear. In eight pigs, implant-associated osteomyelitis was induced on day 0, using a Staphylococcus aureus strain. Following administration of 1,000 mg of vancomycin on day 5, vancomycin concentrations were obtained with microdialysis for 8 h in the implant bone cavity, in cancellous bone adjacent to the implant cavity, in subcutaneous adipose tissue (SCT) adjacent to the implant cavity, and in healthy cancellous bone and healthy SCT in the contralateral leg. Venous blood samples were also obtained. The extent of infection and inflammation was evaluated by post-mortem computed tomography scans, C-reactive protein serum levels and cultures of blood and swabs. In relation to all the implant cavities, bone destruction was found. Ranging from 0.20 to 0.74, tissue penetration, expressed as the ratio of the area under the concentration-time curve from 0 to the last measured value, was incomplete for all compartments except for healthy SCT. The lowest penetration was found in the implant cavity. In conclusion, Staphylococcus aureus implant-associated osteomyelitis was found to reduce vancomycin bone penetration, especially in the implant cavity. These findings suggest that it may be unsafe to rely solely on vancomycin therapy when treating acute osteomyelitis. Particularly when metaphyseal cavities are present, surgical debridement seems necessary. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1093-1098, 2018.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

“…2013/15‐2934‐00946). The study was performed on a previously described osteomyelitis porcine model and analogous to a former study where cefuroxime was the study drug …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Single‐dose bone pharmacokinetics of vancomycin in a porcine implant‐associated osteomyelitis model

Bue

Hanberg

Koch

et al. 2017

Journal Orthopaedic Research

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Innovations in osteomyelitis research: A review of animal models

Roux

Cobb

Seitz

et al. 2021

Anim Models and Exp Med

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Infection of bone tissue, or osteomyelitis, has become a growing concern in modern healthcare due in no small part to a rise in antibiotic resistance among bacteria, notably Staphylococcus aureus. The current standard of care involves aggressive, prolonged antibiotic therapy combined with surgical debridement of infected tissues. While this treatment may be sufficient for resolving a portion of cases, recurrences of the infection and associated risks including toxicity with long‐term antibiotic usage have been reported. Therefore, there exists a need to produce safer, more efficacious options of treatment for osteomyelitis. In order to test treatment regimens, animal models that closely mimic the clinical condition and allow for accurate evaluation of therapeutics are necessary. Establishing a model that replicates features of osteomyelitis in humans continues to be a challenge to scientists, as there are many variables involved, including choosing an appropriate species and method to establish infection. This review addresses the refinement of animal models of osteomyelitis to reflect the clinical disease and test prospective therapeutics. The aim of this review is to explore studies regarding the use of animals for osteomyelitis therapeutics research and encourage further development of such animal models for the translation of results from the animal experiment to human medicine.

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Local concentrations of gentamicin obtained by microdialysis after a controlled application of a GentaColl sponge in a porcine model

Thomassen

Hanberg

Stilling

et al. 2020

Journal Orthopaedic Research

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Local treatment with gentamicin may be an important tool in the prevention and treatment of surgical site infections in high‐risk procedures and patients. The aim of this study was to evaluate the pharmacokinetic profile of gentamicin in bone and surrounding tissue, released from a controlled application of a GentaColl sponge in a porcine model. In eight female pigs, a GentaColl sponge of 10 × 10 cm (1.3 mg gentamicin/cm2) was placed in a cancellous bone cavity in the proximal tibia. Microdialysis was used for sampling of gentamicin concentrations over 48 hours from the cavity with the implanted GentaColl sponge, cancellous bone parallel to the cavity over and under the epiphyseal plate, cortical bone, the intramedullary canal, subcutaneous tissue, and the joint cavity of the knee. Venous blood samples were obtained as reference. The main finding was a mean peak drug concentration (95% CI) of gentamicin in the cancellous bone cavity containing the implanted GentaColl sponge of 11 315 (9049‐13 581) μg/mL, persisting above 1000 μg/mL until approximately 40 hours after application. Moreover, the concentrations were low (<1 μg/mL) in the surrounding tissues as well as in plasma. The mean peak gentamicin concentration from the cancellous bone cavity after a controlled application of a GentaColl sponge was high and may be adequate for the prevention of biofilm formation. However, high MIC strains and uncontrolled application of the GentaColl sponge may jeopardize this conclusion.

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Novel porcine model of implant‐associated osteomyelitis: A comprehensive analysis of local, regional, and systemic response

Cited by 34 publications

References 32 publications

Single‐dose bone pharmacokinetics of vancomycin in a porcine implant‐associated osteomyelitis model

Single‐dose bone pharmacokinetics of vancomycin in a porcine implant‐associated osteomyelitis model

Innovations in osteomyelitis research: A review of animal models

Local concentrations of gentamicin obtained by microdialysis after a controlled application of a GentaColl sponge in a porcine model

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