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

Abstract

The goal of this project is to develop novel methods for the prevention and treatment of orthopaedic infections following traumatic injuries including those incurred on the battlefield. Using Staphylococcus aureus as a proof-of-principle pathogen based on its prominence as a cause of such infections and the severity of the infections its causes, we have undertaken studies to identify the most efficacious antibiotics and investigate the ability to conjugate these antibiotics to a novel bone targeting agent derived from a tetracycline moiety that binds hydroxyapatite. We have also demonstrated that the staphylococcal accessory regulator (sarA) plays a key role in the pathogenesis of orthopaedic infections owing in part to its impact on biofilm formation and intrinsic antibiotic resistance. Based on this, we have undertaken a search for small molecule inhibitors that could be used alone or in combination with conventional antibiotics and our bone targeting agent. Ultimately, these combinations will be evaluated based on their therapeutic efficacy in established animal models of traumatic bone infection.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2018
Accession Number
AD1093710

Entities

People

  • Mark S Smeltzer

Organizations

  • University of Arkansas System

Tags

DTIC Thesaurus Topics

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Arkansas
  • Bacteria
  • Bacteriology
  • Biomedical Research
  • Chemical Synthesis
  • Chemistry
  • Chemotherapy
  • Gram-Negative Bacteria
  • Health Services
  • Infection
  • Lipopeptides
  • Microbiology
  • Small Molecules
  • Staphylococcus Aureus
  • Universities

Fields of Study

  • Medicine

Readers

  • Microbial Pathology
  • Oncology (Cancer Research).
  • Trauma Surgery or Emergency Medicine.

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech