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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 41 - 41
24 Nov 2023
Lilleøre JG Jørgensen A Knudsen M Hanberg P Öbrink-Hansen K Tøstesen S Søballe K Stilling M Bue M
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Background and aim

Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low it is crucial to achieve adequate antibiotic concentrations proximate to the implant for a sufficient amount of time to protect the implant surface and ensure tissue integration. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant inserted in cancellous bone.

Method

Six female pigs received an intravenous bolus infusion of 4 g/0.5 g piperacillin/tazobactam over 30 min every 6 h. Steady state was assumed achieved in the third dosing interval (12–18 h). Microdialysis catheters were placed in a cannulated screw in the proximal tibial cancellous bone, in cancellous bone next to the screw, and in cancellous bone on the contralateral tibia. Dialysates were collected from time 12 to 18 h and plasma samples were collected as reference.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 61 - 61
1 Dec 2021
Hanberg P Bue M Öbrink-Hansen K Thomassen M S⊘balle K Stilling M
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Aim

Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios.

Method

Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration.


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).


Bone & Joint Research
Vol. 10, Issue 1 | Pages 60 - 67
1 Jan 2021
Bendtsen MAF Bue M Hanberg P Slater J Thomassen MB Hansen J Søballe K Öbrink-Hansen K Stilling M

Aims

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

Methods

A total of 16 pigs were randomly allocated to either intravenous (Group IV) or oral (Group PO) flucloxacillin 1 g every six hours during a 24-hour period. 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).


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 91 - 91
1 Dec 2020
Hanberg P Bue M Öbrink-Hansen K Thomassen M S⊘balle K Stilling M
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Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios.

Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration.

Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 μg/mL) in calcaneal cancellous bone and subcutaneous tissue throughout the 90 min tourniquet duration in Group A and B. Cefuroxime administration at tourniquet release (Group C) resulted in concentrations above 4 μg/mL for a minimum of 3.5 hours in the tissues on the tourniquet side. There were no significant differences in the T>MIC (4 μg/mL) in subcutaneous tissue or calcaneal cancellous bone between the three groups. However, Group A tended toward shorter T>MIC in tourniquet calcaneal cancellous bone compared to Group C (p=0.08).

We conclude that administration of cefuroxime (1.5 g) in the 15–45 min window prior to tourniquet inflation resulted in sufficient calcaneal cancellous bone and subcutaneous tissue concentrations throughout the 90 min tourniquet application. If the target is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at tourniquet release.