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Orthopaedic Proceedings

Vol. 100-B, Issue SUPP_17 | Pages 45 - 45

1 Dec 2018

SINGLE-DOSE BONE PHARMACOKINETICS OF VANCOMYCIN IN A PORCINE IMPLANT-ASSOCIATED OSTEOMYELITIS MODEL

Bue M Hanberg P Koch J Jensen LK Lundorff M Aalbæk B Jensen HE Søballe K Tøttrup M

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Aim

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. We assessed the effect of a traumatically induced, implant-associated acute osteomyelitis on vancomycin bone penetration in a porcine model.

Method

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 eight hours 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.

Orthopaedic Proceedings

Vol. 98-B, Issue SUPP_23 | Pages 77 - 77

1 Dec 2016

INFECTED BONE TISSUE DECREASES THE PENETRATION OF CEFUROXIME

Tøttrup M Bue M Koch J Jensen LK Hanberg P Aalbæk B Fuursted K Jensen HE Søballe K

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Aim

A reason for treatment failure, in cases of periprosthetic bone infections and osteomyelitis, may be incomplete or heterogeneous tissue distribution of antimicrobials to the affected bone. Decreased bioavailability has been demonstrated in healthy bones but never in pathological bone tissue. Therefore, the aim was to obtain pharmacokinetic parameters of cefuroxime in infected bone tissue by means of microdialysis in a porcine model of implant associated osteomyelitis

Method

An implant cavity of 4 mm in diameter was drilled 25 mm into the right tibial bone of ten pigs (30 kg/BW). Subsequently, a small steel implant (K-wire 2 × 2 mm) and 10⁴ CFU of Staphylococcus aureus was inserted and injected into the implant cavity. Five days after inoculation, two additional drill holes of 2 × 25 mm were drilled into the trabecular bone tissue adjacent to the implant cavity and into the left uninfected tibia. After intravenous administration of 1500 mg of cefuroxime, the concentration was measured in plasma and in the three tibial drill holes for 8 hours. All measurements were performed with microdialysis. Post mortem, the presence of bone infection was assessed by computed tomography (CT) scans and cultures of swabs.

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