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Concentrations of Co-Administered Meropenem and Vancomycin in Spinal Tissues Relevant for the Treatment of Pyogenic

Josefine Slater1,2,3, Maiken Stilling1,2,3, Pelle Hanberg1,3

  • 1Department of Orthopaedic Surgery, Aarhus University Hospital, 8200 Aarhus, Denmark.

Antibiotics (Basel, Switzerland)
|May 27, 2023
PubMed

Insights

Co-administering meropenem and vancomycin for pyogenic spondylodiscitis showed varied spinal tissue concentrations. Dosing may need adjustment to ensure adequate antibiotic levels against bacteria in bone and disc infections.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Surgical Infections

Background:

  • Pyogenic spondylodiscitis treatment often involves empirical antibiotics like meropenem and vancomycin.
  • Systemic co-administration aims to achieve therapeutic drug concentrations in spinal tissues.
  • Evaluating drug penetration into spinal tissues is crucial for optimizing treatment efficacy.

Purpose of the Study:

  • To assess the time above minimal inhibitory concentration (%T>MIC) for meropenem and vancomycin in porcine spinal tissues.
  • To compare drug concentrations in vertebral bone, intervertebral discs, muscle, and plasma.
  • To determine the influence of MIC targets on %T>MIC in different spinal compartments.

Main Methods:

  • Utilized an experimental porcine model to simulate pyogenic spondylodiscitis treatment.
  • Administered a single dose of meropenem (1000 mg) and vancomycin (1000 mg) intravenously.
  • Employed microdialysis in cervical vertebral bone, intervertebral disc, paravertebral muscle, and subcutaneous tissue for drug concentration analysis.
  • Collected plasma samples for reference pharmacokinetic data.

Main Results:

  • %T>MIC values were highly dependent on the selected minimal inhibitory concentration (MIC) target for both antibiotics.
  • Significant heterogeneity in %T>MIC was observed across all investigated spinal tissues.
  • Meropenem showed lower %T>MIC in vertebral bone, while vancomycin had lower %T>MIC in the intervertebral disc.
  • Plasma exhibited the highest %T>MIC for both drugs, indicating better systemic than local tissue penetration.

Conclusions:

  • Current dosing of meropenem and vancomycin may not consistently achieve target %T>MIC in spinal tissues for spondylodiscitis.
  • Heterogeneous drug distribution necessitates consideration of MIC variability and tissue penetration.
  • A more aggressive dosing strategy for meropenem and vancomycin might be required to ensure effective treatment of spinal infections.
Keywords:
antibiotic stewardshipmeropenemmicrodialysispharmacodynamicspharmacokineticsspinal tissuesspondylodiscitistarget sitevancomycin

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