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Piperacillin Steady State Concentrations in Target Tissues Relevant for PJI Treatment-A Randomized Porcine

Hans Christian Rasmussen1,2, Pelle Hanberg1,2, Martin Knudsen1,2

  • 1Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.

Antibiotics (Basel, Switzerland)
|March 29, 2023
PubMed
Summary

Continuous piperacillin infusion achieved higher concentrations above the minimum inhibitory concentration (MIC) in target tissues for periprosthetic joint infections (PJI) compared to intermittent infusion. This suggests continuous infusion may be more effective for treating PJI caused by Pseudomonas aeruginosa.

Keywords:
Pseudomonas aeruginosamicrodialysispharmacokineticspiperacillinporcine modelprosthetic joint infections

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Area of Science:

  • Pharmacokinetics and Pharmacodynamics
  • Infectious Diseases
  • Orthopedic Surgery

Background:

  • Piperacillin is a key antibiotic for treating periprosthetic joint infections (PJI) caused by Pseudomonas aeruginosa.
  • Optimizing piperacillin dosing is crucial for effective PJI treatment, particularly achieving adequate drug concentrations in relevant tissues.

Purpose of the Study:

  • To compare the time above minimum inhibitory concentration (fT > MIC) of piperacillin in key tissues for PJI treatment.
  • To evaluate the impact of continuous versus intermittent short-term infusion on piperacillin tissue concentrations at steady state.

Main Methods:

  • A randomized study involving 16 pigs receiving either continuous or intermittent short-term piperacillin infusion.
  • Microdialysis was used to measure steady-state piperacillin concentrations in tibial bone (cortical and cancellous), synovial fluid, and subcutaneous tissue.
  • Plasma concentrations served as a reference, with MIC targets of 4, 8, 16, and 64 mg/L applied.

Main Results:

  • Continuous infusion led to significantly longer fT > MIC for lower MIC targets (4 and 8 mg/L) across most tissues, excluding tibial cortical bone.
  • For a higher MIC target (16 mg/L), continuous infusion maintained longer fT > MIC in non-bone compartments.
  • No significant differences in fT > MIC were observed between infusion methods at the highest MIC target (64 mg/L).

Conclusions:

  • Achieving sufficient piperacillin concentrations in bone compartments for PJI treatment may require aggressive dosing strategies, especially with higher MIC targets.
  • Continuous piperacillin infusion is a potentially superior administration method for managing PJI compared to intermittent short-term infusion.