Enhancing the Prevention and Treatment of Orthopaedic Infections Associated with Traumatic Injury

Abstract

Injuries to the bone resulting from traumatic injury are highly susceptible to infection, and the resulting infections are therapeutically recalcitrant to antibiotic therapy. The overall goal of this project was to develop improved treatment methods that could be used to overcome this therapeutic recalcitrance. To this end, we evaluated existing antibiotics based on their efficacy in the specific context of a biofilm, took advantage of our knowledge regarding the pathogenesis of Staphylococcus aureus as a cause of bone infection to identify small molecule inhibitors of the staphylococcal accessory regulator (sarA), and explored methods to enhance the systemic delivery of the most efficacious antibiotics and effective sarA inhibitors directly to the bone. The ultimate goal was to then evaluate the efficacy of these novel approaches, alone and in combination with each other, in a relevant animal model of posttraumatic osteomyelitis. The first of these objectives was accomplished, and the second and third were extensively explored at an antimicrobial, anti-biofilm, and pharmacological basis.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2019
Accession Number
AD1097747

Entities

People

  • Mark S Smeltzer

Organizations

  • University of Arkansas for Medical Sciences

Tags

DTIC Thesaurus Topics

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Bacteria
  • Bone And Bones
  • Bone Diseases
  • Chemical Synthesis
  • Chemistry
  • Health Services
  • Medical Personnel
  • Organic Chemistry

Fields of Study

  • Medicine

Readers

  • Immunology and Pathology
  • Microbial Pathology
  • Oncology

Technology Areas

  • Biotechnology