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Intravenous Cefazolin Achieves Sustained High Interstitial Concentrations in Open Lower Extremity Fractures.

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Area of Science:

  • Orthopedic surgery
  • Infectious disease
  • Pharmacokinetics

Background:

  • Open fractures pose a significant infection risk despite standard treatment.
  • Antibiotic pharmacokinetics in open fracture sites are not well understood.
  • Direct sampling is needed to characterize antibiotic concentrations in injured tissues.

Purpose of the Study:

  • To evaluate cefazolin concentration and pharmacokinetics in open fracture sites.
  • To compare antibiotic delivery in injured versus uninjured limbs.

Main Methods:

  • Observational study of eight adult patients with open fractures.
  • Microdialysis catheters placed in injured and contralateral limbs.
  • Cefazolin levels measured in interstitial fluid and plasma over 24 hours.
  • Pharmacokinetic analysis using noncompartmental methods.

Main Results:

  • No significant difference in 24-hour cefazolin exposure (fAUC0-24hrs) between injured and uninjured limbs.
  • Time to maximum concentration (fTmax) of cefazolin was delayed in injured limbs (p=0.046).
  • Cefazolin concentrations remained above the Staphylococcus aureus MIC for 100% of the time in both limb types.

Conclusions:

  • Current cefazolin dosing achieves adequate antibiotic levels at open fracture sites (Gustilo-Anderson Types II and IIIA).
  • Delayed cefazolin delivery to injured tissue is observed but does not compromise antimicrobial effectiveness.
  • Further studies are needed for higher-grade open fractures (Types IIIB and IIIC).