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Published on: August 30, 2018
Steady-State Piperacillin Concentrations in the Proximity of an Orthopedic Implant: A Microdialysis Porcine Study
Johanne Gade Lilleøre1,2, Andrea René Jørgensen1,2, Martin Bruun Knudsen1,2
1Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark.
Abstract:
Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low, sufficient antibiotic protection of the implant surface is important. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant. Time above the minimal inhibitory concentration (fT>MIC) was evaluated for MIC of 8 (low target) and 16 μg/mL (high target). 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. For the low piperacillin target (8 µg/mL), comparable mean fT>MIC across all the investigated compartments (mean range: 54-74%) was found. For the high target (16 µg/mL), fT>MIC was shorter inside the cannulated screw (mean: 16%) than in the cancellous bone next to the screw and plasma (mean range: 49-54%), and similar between the two cancellous bone compartments. To reach more aggressive piperacillin fT>MIC targets in relation to the implant, alternative dosing regimens such as continuous infusion may be considered.
Insights
This study assessed piperacillin concentrations near orthopedic implants. Achieving high antibiotic targets (16 µg/mL) was challenging within the implant, suggesting continuous infusion may improve outcomes for preventing implant-associated osteomyelitis.
Area of Science:
- Orthopedic Surgery
- Pharmacokinetics
- Infectious Disease
Background:
- Implant-associated osteomyelitis is a significant complication of orthopedic surgery.
- Maintaining adequate antibiotic concentrations at the implant surface is crucial for prevention.
- Piperacillin is a commonly used antibiotic for surgical prophylaxis.
Purpose of the Study:
- To evaluate steady-state piperacillin concentrations near orthopedic implants.
- To determine the time above the minimal inhibitory concentration (fT>MIC) for piperacillin at different targets.
- To assess the impact of implant proximity on antibiotic efficacy.
Main Methods:
- Utilized a porcine model with orthopedic implants.
- Administered piperacillin/tazobactam via intravenous bolus infusion every 6 hours.
- Employed microdialysis to measure piperacillin concentrations in bone and plasma.
- Calculated fT>MIC for piperacillin at 8 µg/mL and 16 µg/mL.
Main Results:
- For a low piperacillin target (8 µg/mL), mean fT>MIC was 54-74% across all compartments.
- For a high target (16 µg/mL), fT>MIC was significantly lower within the implant (16%) compared to surrounding bone and plasma (49-54%).
- Achieving high piperacillin targets within the implant was challenging with standard dosing.
Conclusions:
- Standard intermittent piperacillin dosing may not achieve optimal fT>MIC targets at the implant surface.
- Continuous infusion or alternative dosing regimens could be considered to enhance antibiotic protection near orthopedic implants.
- Further research is needed to optimize antibiotic strategies for preventing implant-associated osteomyelitis.
