Systemic versus free antibiotic delivery in preventing acute exogenous implant related infection in a rat model

Scott Marston, Gudrun Mirick Mueller, Arick Sabin, Glen T. Hansen, Bruce Lindgren, Conrado Aparicio, Alexandra R. Armstrong, Ole H. Larsen, Andrew Schmidt, Richard Kyle, Ramon Gustilo, Dean Tsukayama, Joan Bechtold, Mats Bue

Research output: Contribution to journalArticlepeer-review

Abstract

We studied systemic ceftriaxone, and free/local tobramycin and doxycycline in a controlled rat model representing a generic acute exogenous joint infection. We hypothesized that evidence of infection (quantitative colony forming units [CFU], qualitative scanning electron microscopy [SEM], histopathology) (1a) would be reduced with local versus systemic antibiotic, (1b) any antibiotic would be superior to control, (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4-week euthanasia. Study groups included infected and noninfected (1) control (no treatment), (2) systemic ceftriaxone (daily), (3) local tobramycin, and (4) local doxycycline (10 rats/group; power = 0.8). With IACUC approval, a reliable acute exogenous joint infection was created by slowly injecting 50-μl, 104 CFU Staphylococcus aureus, into the distal femoral medullary canal. The antibiotic formulation was introduced locally to the femoral canal and joint space. After 4 weeks, serum, pin, bone, and synovium were obtained. CFU/ml of bone and synovium were quantified using macrotiter method. SEM imaged biofilm on the surface of the pin, histopathology identified tissue response, liquid chromatography/mass spectrometry quantified plasma antibiotic. (1) Groups receiving any antibiotic reported lower CFU/ml in synovium compared with no treatment. (2) In the synovium, free/local tobramycin reduced CFU/ml to a greater extent than free/local doxycycline (p < 0.05). (3) Antibiotic in plasma after the local application was nondetectable in all groups after 4 weeks. SEM revealed no difference in biofilm on pin among all groups.

Original languageEnglish (US)
JournalJournal of Orthopaedic Research
DOIs
StateAccepted/In press - 2021

Bibliographical note

Funding Information:
The authors would like to thank Myra Rusten, Toni Meglitsch, and Barbara Wicklund for their surgical assistance and study facilitation as well as Ruoqiong Chen for her assistance with SEM imaging. This study was funded by NIH Clinical Center (Grant no. NIH R21AI115416‐0).

Publisher Copyright:
© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC

Keywords

  • bone infection
  • doxycycline
  • local antibiotics
  • prevention
  • prosthetic joint infection
  • tobramycin

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