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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 27 - 27
1 Oct 2022
Vittrup S Jensen LK Hanberg P Slater J Hvistendahl MA Stilling M Jørgensen N Bue M
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Aim

This study investigated if co-administration of rifampicin with moxifloxacin led to a decrease in moxifloxacin concentrations in relevant tissues in a porcine model of implant-associated osteomyelitis caused S. aureus. Pharmacokinetics were measured using microdialysis and treatment effect was measured by quantifying bacterial load from implant and periprosthetic bone following a 1-stage revision and antibiotics.

Method

15 female pigs received a stainless-steel implant in the right proximal tibia and were randomized into two groups. Infection was introduced by inoculating the implant with Staphylococcus aureus as previously described1. On day 7 post surgery, all pigs were revised with implant removal, debridement of implant cavity and insertion of a sterile implant. 7 days of treatment was then initiated with either moxifloxacin 400 mg iv q.d. (M) or moxifloxacin and rifampicin 450 mg iv b.i.d. (RM). At day 14, animals were sedated and microdialysis was applied for continuous sampling of moxifloxacin concentrations during 8 h in five compartments: the implant cavity, cancellous bone in both the infected and non-infected proximal tibia, and adjacent subcutaneous tissue on both the infected and non-infected side using a previously described setup2. Venous blood samples were collected. Implant and adjacent bone were removed for analysis.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 41 - 41
1 Dec 2021
Kipp JO Hanberg P Slater J Nielsen LM Jakobsen SS Stilling M Bue M
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Background

Systemically administered vancomycin may provide insufficient target-site concentrations. Intraosseous vancomycin administration has the potential to overcome this concern by providing high target-site concentrations.

Aim

To evaluate the local bone and tissue concentrations following tibial intraosseous vancomycin administration in a porcine model.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 52 - 52
1 Dec 2021
Slater J Hanberg P Bendtsen MAF J⊘rgensen AR Greibe E S⊘balle K Bue M J⊘rgensen N Stilling M
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Aim

Pyogenic spondylodiscitis remains a therapeutic challenge, as demonstrated by divergent treatment guidelines. The combination of moxifloxacin and rifampicin may be an attractive treatment option for cases caused by staphylococci; however, previous studies have reported a reduction in plasma concentrations of moxifloxacin when co-administered with rifampicin. The magnitude of this reduction in spinal tissues is not known. We aimed to investigate the interaction of rifampicin on moxifloxacin tissue concentrations in vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue in steady-state conditions using microdialysis in a porcine model.

Method

Twenty female pigs were randomized into two groups of ten pigs: Group A received moxifloxacin 400 mg orally once daily for three days preoperatively. Group B received moxifloxacin 400 mg orally for three days preoperatively combined with rifampicin 450 mg twice daily for seven days preoperatively. Measurements were obtained from plasma, vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue for 24 h. Microdialysis was applied for sampling in solid tissues.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_5 | Pages 8 - 8
1 Mar 2021
Bendtsen MAF Bue M Hanberg P Slater J Thomassen M Hansen J S⊘balle K Öbrink-Hansen K Stilling M
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Aim

Flucloxacillin is conventionally administered intravenously for perioperative prophylaxis, while oral administration is typical for bacterial inoculation prophylaxis following smaller traumatic wounds. We aimed to assess the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration (fT>MIC) for meticillin-susceptible Staphylococcus aureus in soft and bone tissue, after intravenous and oral administration, using microdialysis in a porcine model.

Method

16 pigs were randomly allocated to either intravenous (Group IV) or oral (Group PO) flucloxacillin 1 g every 6 h during 24 h. Microdialysis was used for sampling in cancellous and cortical bone, subcutaneous tissue, and the knee joint. In addition, plasma was sampled. The flucloxacillin fT>MIC was evaluated using a low MIC target (0.5 μg/mL) and a high MIC target (2.0 μg/mL).