Antimicrobial distribution from local delivery depends on dose : a pilot study with MRI

Clin Orthop Relat Res. 2014 Nov;472(11):3324-9. doi: 10.1007/s11999-014-3493-1.

Abstract

Background: Tissue distribution after local delivery has been quantified over a period of 5 hours on 7-T MRI in a rabbit model using gadolinium-labeled diethylenetriamine pentaacetic acid (Gd-DTPA) as an antimicrobial surrogate; however, it is unknown how the Gd-DTPA load in a local depot will affect the duration of high-concentration Gd-DTPA in local tissues after surgical débridement.

Questions/purposes: We determined whether the Gd-DTPA load in bone cement affected its local tissue distribution over a period of 1 month after local delivery.

Methods: A 1-cm3 soft tissue dead space was created in the quadriceps of seven rabbits and filled with gadolinium-loaded bone cement. At 7, 14, and 33 days, the volume of tissue with a Gd-DTPA concentration of more than 14 μg/mL was calculated from T1-weighted images using 7-T MRI. Differences in volumes of distribution were analyzed with ANOVA.

Results: The volume of tissue with more than 14 μg/mL Gd-DTPA was much larger from higher gadolinium loads on Day 7 (p=0.02) (2121 mm3 for 10 g and 665 mm3 for 1 g) and smaller with time for the 10-g formulation (2121 mm3 on Day 7 and 1241 mm3 on Day 14).

Conclusions: Volume of distribution and duration of Gd-DTPA after local delivery increased with increasing load in the cement and decreased with time.

Clinical relevance: For local delivery, high antimicrobial concentrations would be expected in greater volumes of tissue, for longer durations, when higher antimicrobial loads are used.

MeSH terms

  • Analysis of Variance
  • Animals
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / pharmacokinetics*
  • Contrast Media / pharmacokinetics*
  • Debridement
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / instrumentation
  • Drug Implants / administration & dosage
  • Drug Implants / pharmacokinetics*
  • Gadolinium DTPA / pharmacokinetics*
  • Magnetic Resonance Imaging / methods
  • Methylmethacrylate / chemistry
  • Models, Animal
  • Pilot Projects
  • Rabbits
  • Thigh / pathology
  • Thigh / surgery
  • Tissue Distribution

Substances

  • Anti-Infective Agents
  • Contrast Media
  • Drug Implants
  • Methylmethacrylate
  • Gadolinium DTPA